Results

NEVER press reload or F5 - unless you want to start from the very beginning.
Input seems to be ok - now mapping the variant to the different transcripts...
Querying Taster for transcript #1: ENST00000637424
Querying Taster for transcript #2: ENST00000636627
Querying Taster for transcript #3: ENST00000481478
Querying Taster for transcript #4: ENST00000288139
Querying Taster for transcript #5: ENST00000350061
Querying Taster for transcript #6: ENST00000636938
Querying Taster for transcript #7: ENST00000636570
Querying Taster for transcript #8: ENST00000422281
Querying Taster for transcript #9: ENST00000640483
MT speed 0.46 s - this script 2.922175 s

Transcript summary:

Permalink

Transcript	Gene symbol	Prediction	Tree vote	Model	Splice site change	Variant type	Protein length	Features at a glance
ENST00000350061(MANE Select)	CACNA1D	Deleterious	75\|25	simple_aae	No	Single base exchange	Normal	Amino acid sequence changed Protein features (might be) affected
ENST00000637424	CACNA1D	Deleterious	84\|16	simple_aae	No	Single base exchange	Normal	Amino acid sequence changed
ENST00000636570	CACNA1D	Deleterious	84\|16	simple_aae	No	Single base exchange	Normal	Amino acid sequence changed
ENST00000422281	CACNA1D	Deleterious	84\|16	simple_aae	No	Single base exchange	Normal	Amino acid sequence changed Protein features (might be) affected
ENST00000481478	CACNA1D	Deleterious	87\|13	simple_aae	No	Single base exchange	Normal	Amino acid sequence changed
ENST00000288139(MANE Select)	CACNA1D	Deleterious	87\|13	simple_aae	No	Single base exchange	Normal	Amino acid sequence changed Protein features (might be) affected
ENST00000640483	CACNA1D	Deleterious	90\|10	simple_aae	No	Single base exchange	Normal	Amino acid sequence changed
ENST00000636627	CACNA1D	Deleterious	91\|9	simple_aae	No	Single base exchange	Normal	Amino acid sequence changed
ENST00000636938	CACNA1D	Deleterious	91\|9	simple_aae	No	Single base exchange	Normal	Amino acid sequence changed

Variant:

3:53723838A>T_5_ENST00000350061

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Protein features (might be) affected

Model: simple_aae
Tree vote: 75|25 (del | benign) ?

Analysed issue

Analysis result

Variant

Chr3:53723838A>T (GRCh38)

Gene symbol

CACNA1D

Gene constraints

LOEUF: 0.25, LOF (oe): 0.19, misssense (oe): 0.64, synonymous (oe): 0.92 ? (gnomAD)

Ensembl transcript ID

ENST00000350061.11

Genbank transcript ID

NM_001128840 (exact from MANE)

UniProt / AlphaMissense peptide

CAC1D_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1939A>T
g.394876A>T

AA changes

AAE:	M647L	?
Score:	15

Frameshift

Length of protein

Normal

Pathogenic variant (ClinVar)

Variant not listed in ClinVar as (likely) pathogenic.

Variant DBs

dbSNP ID	rs368260280
gnomAD	homozygous (T/T)	heterozygous	allele carriers
	0	74	74

Protein conservation

Species	Match	AA	Alignment
Human		647	L	S	N	L	V	A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F	L
mutated	all conserved	647	L	S	N	L	V	A	S	L	L	N	S	L	K	S	I	A	S	L	L	L	L	L	F
Ptroglodytes	all identical	667						A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F
Mmulatta	all identical	667						A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F
Fcatus	all identical	667						A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F
Mmusculus	all identical	675	L	S	N	L	V	A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F
Ggallus	all identical	668					V	A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F
Trubripes	all identical	648	L	S	N	L	V	A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	all identical	664	L	S	N	L	V	A	S	L	L	N	S	M	K	S	I	A	S

Protein features

Start (aa)	End (aa)	Feature	Details
1	2161	CHAIN		lost
509	755	REPEAT	II	lost
634	652	TOPO_DOM	Cytoplasmic	lost
647	672	HELIX		lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	2.735	1
	6.318	1
(flanking)	8.017	1

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

Strand

Original gDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered gDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Original cDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered cDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Wildtype AA sequence

MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
ITMEGWTDVL YWMNDAMGFE LPWVYFVSLV IFGSFFVLNL VLGVLSGEFS KEREKAKARG
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
GEGENRGCCG SLCQAISKSK LSRRWRRWNR FNRRRCRAAV KSVTFYWLVI VLVFLNTLTI
SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ AYFVSLFNRF DCFVVCGGIT
ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV ASLLNSMKSI ASLLLLLFLF
IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ ILTGEDWNAV MYDGIMAYGG
PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES LNTAQKEEAE EKERKKIARK
ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP CDVPVGEEEE EEEEDEPEVP
AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH KLINHHIFTN LILVFIMLSS
AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT FGAFLHKGAF CRNYFNLLDM
LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG LKHVVQCVFV AIRTIGNIMI
VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI LYKDGDVDSP VVRERIWQNS
DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP IYNHRVEISI FFIIYIIIVA
FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL KARPLRRYIP KNPYQYKFWY
VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL NMVFTGVFTV EMVLKVIAFK
PKGYFSDAWN TFDSLIVIGS IIDVALSEAD PTESENVPVP TATPGNSEES NRISITFFRL
FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL PYVALLIAML FFIYAVIGMQ MFGKVAMRDN
NQINRNNNFQ TFPQAVLLLF RCATGEAWQE IMLACLPGKL CDPESDYNPG EEYTCGSNFA
IVYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH HLDEFKRIWS EYDPEAKGRI
KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVAMNMPLNS DGTVMFNATL FALVRTALKI
KTEGNLEQAN EELRAVIKKI WKKTSMKLLD QVVPPAGDDE VTVGKFYATF LIQDYFRKFK
KRKEQGLVGK YPAKNTTIAL QAGLRTLHDI GPEIRRAISC DLQDDEPEET KREEEDDVFK
RNGALLGNHV NHVNSDRRDS LQQTNTTHRP LHVQRPSIPP ASDTEKPLFP PAGNSVCHNH
HNHNSIGKQV PTSTNANLNN ANMSKAAHGK RPSIGNLEHV SENGHHSSHK HDREPQRRSS
VKRTRYYETY IRSDSGDEQL PTICREDPEI HGYFRDPHCL GEQEYFSSEE CYEDDSSPTW
SRQNYGYYSR YPGRNIDSER PRGYHHPQGF LEDDDSPVCY DSRRSPRRRL LPPTPASHRR
SSFNFECLRR QSSQEEVPSS PIFPHRTALP LHLMQQQIMA VAGLDSSKAQ KYSPSHSTRS
WATPPATPPY RDWTPCYTPL IQVEQSEALD QVNGSLPSLH RSSWYTDEPD ISYRTFTPAS
LTVPSSFRNK NSDKQRSADS LVEAVLISEG LGRYARDPKF VSATKHEIAD ACDLTIDEME
SAASTLLNGN VRPRANGDVG PLSHRQDYEL QDFGPGYSDE EPDPGRDEED LADEMICITT
L*

Mutated AA sequence

MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
ITMEGWTDVL YWMNDAMGFE LPWVYFVSLV IFGSFFVLNL VLGVLSGEFS KEREKAKARG
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
GEGENRGCCG SLCQAISKSK LSRRWRRWNR FNRRRCRAAV KSVTFYWLVI VLVFLNTLTI
SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ AYFVSLFNRF DCFVVCGGIT
ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV ASLLNSLKSI ASLLLLLFLF
IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ ILTGEDWNAV MYDGIMAYGG
PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES LNTAQKEEAE EKERKKIARK
ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP CDVPVGEEEE EEEEDEPEVP
AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH KLINHHIFTN LILVFIMLSS
AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT FGAFLHKGAF CRNYFNLLDM
LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG LKHVVQCVFV AIRTIGNIMI
VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI LYKDGDVDSP VVRERIWQNS
DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP IYNHRVEISI FFIIYIIIVA
FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL KARPLRRYIP KNPYQYKFWY
VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL NMVFTGVFTV EMVLKVIAFK
PKGYFSDAWN TFDSLIVIGS IIDVALSEAD PTESENVPVP TATPGNSEES NRISITFFRL
FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL PYVALLIAML FFIYAVIGMQ MFGKVAMRDN
NQINRNNNFQ TFPQAVLLLF RCATGEAWQE IMLACLPGKL CDPESDYNPG EEYTCGSNFA
IVYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH HLDEFKRIWS EYDPEAKGRI
KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVAMNMPLNS DGTVMFNATL FALVRTALKI
KTEGNLEQAN EELRAVIKKI WKKTSMKLLD QVVPPAGDDE VTVGKFYATF LIQDYFRKFK
KRKEQGLVGK YPAKNTTIAL QAGLRTLHDI GPEIRRAISC DLQDDEPEET KREEEDDVFK
RNGALLGNHV NHVNSDRRDS LQQTNTTHRP LHVQRPSIPP ASDTEKPLFP PAGNSVCHNH
HNHNSIGKQV PTSTNANLNN ANMSKAAHGK RPSIGNLEHV SENGHHSSHK HDREPQRRSS
VKRTRYYETY IRSDSGDEQL PTICREDPEI HGYFRDPHCL GEQEYFSSEE CYEDDSSPTW
SRQNYGYYSR YPGRNIDSER PRGYHHPQGF LEDDDSPVCY DSRRSPRRRL LPPTPASHRR
SSFNFECLRR QSSQEEVPSS PIFPHRTALP LHLMQQQIMA VAGLDSSKAQ KYSPSHSTRS
WATPPATPPY RDWTPCYTPL IQVEQSEALD QVNGSLPSLH RSSWYTDEPD ISYRTFTPAS
LTVPSSFRNK NSDKQRSADS LVEAVLISEG LGRYARDPKF VSATKHEIAD ACDLTIDEME
SAASTLLNGN VRPRANGDVG PLSHRQDYEL QDFGPGYSDE EPDPGRDEED LADEMICITT
L*

Position of stopcodon in wt / mu CDS

6486 / 6486

Position (AA) of stopcodon in wt / mu AA sequence

2162 / 2162

Position of stopcodon in wt / mu cDNA

7042 / 7042

Position of start ATG in wt / mu cDNA

557 / 557

Last intron/exon boundary

6748

Theoretical NMD boundary in CDS

6141

Length of CDS

6486

Coding sequence (CDS) position

1939

cDNA position

2495

gDNA position

394876

Chromosomal position

53723838

Speed

0.06 s

All positions are in basepairs (bp) if not explicitly stated differently. cDNA/gDNA/chromosomal position: Ins/del are shown as 'last normal base / first normal base'.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project

Back to summary table

Variant:

3:53723838A>T_1_ENST00000637424

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed

Model: simple_aae
Tree vote: 84|16 (del | benign) ?

Analysed issue

Analysis result

Variant

Chr3:53723838A>T (GRCh38)

Gene symbol

CACNA1D

Gene constraints

LOEUF: 0.26, LOF (oe): 0.20, misssense (oe): 0.63, synonymous (oe): 0.92 ? (gnomAD)

Ensembl transcript ID

ENST00000637424.1

Genbank transcript ID

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.2011A>T
g.394876A>T

AA changes

AAE:	M671L	?
Score:	15

Frameshift

Length of protein

Normal

Pathogenic variant (ClinVar)

Variant not listed in ClinVar as (likely) pathogenic.

Variant DBs

dbSNP ID	rs368260280
gnomAD	homozygous (T/T)	heterozygous	allele carriers
	0	74	74

Protein conservation

Species	Match	AA	Alignment
Human		671	L	S	N	L	V	A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F	L
mutated	all conserved	671		S	N	L	V	A	S	L	L	N	S	L	K	S	I	A	S	L	L	L	L	L	F
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

N/A

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	2.735	1
	6.318	1
(flanking)	8.017	1

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

Strand

Original gDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered gDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Original cDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered cDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Wildtype AA sequence

MEMNLPTFSS DLIFIKSTMY QEIDARYKGK VISEAETKGY FSLAFGEANY ARGTRLPLSG
EGPTSQPNSS KQTVLSWQAA IDAARQAKAA QTMSTSAPPP VGSLSQRKRQ QYAKSKKQGN
SSNSRPARAL FCLSLNNPIR RACISIVEWK PFDIFILLAI FANCVALAIY IPFPEDDSNS
TNHNLEKVEY AFLIIFTVET FLKIIAYGLL LHPNAYVRNG WNLLDFVIVI VGLFSVILEQ
LTKETEGGNH SSGKSGGFDV KALRAFRVLR PLRLVSGVPS LQVVLNSIIK AMVPLLHIAL
LVLFVIIIYA IIGLELFIGK MHKTCFFADS DIVAEEDPAP CAFSGNGRQC TANGTECRSG
WVGPNGGITN FDNFAFAMLT VFQCITMEGW TDVLYWVNDA IGWEWPWVYF VSLIILGSFF
VLNLVLGVLS GEFSKEREKA KARGDFQKLR EKQQLEEDLK GYLDWITQAE DIDPENEEEG
GEEGKRNTSM PTSETESVNT ENVSGEGENR GCCGSLCQAI SKSKLSRRWR RWNRFNRRRC
RAAVKSVTFY WLVIVLVFLN TLTISSEHYN QPDWLTQIQD IANKVLLALF TCEMLVKMYS
LGLQAYFVSL FNRFDCFVVC GGITETILVE LEIMSPLGIS VFRCVRLLRI FKVTRHWTSL
SNLVASLLNS MKSIASLLLL LFLFIIIFSL LGMQLFGGKF NFDETQTKRS TFDNFPQALL
TVFQILTGED WNAVMYDGIM AYGGPSSSGM IVCIYFIILF ICGNYILLNV FLAIAVDNLA
DAESLNTAQK EEAEEKERKK IARKESLENK KNNKPEVNQI ANSDNKVTID DYREEDEDKD
PYPPCDVPVG EEEEEEEEDE PEVPAGPRPR RISELNMKEK IAPIPEGSAF FILSKTNPIR
VGCHKLINHH IFTNLILVFI MLSSAALAAE DPIRSHSFRN TILGYFDYAF TAIFTVEILL
KMTTFGAFLH KGAFCRNYFN LLDMLVVGVS LVSFGIQSSA ISVVKILRVL RVLRPLRAIN
RAKGLKHVVQ CVFVAIRTIG NIMIVTTLLQ FMFACIGVQL FKGKFYRCTD EAKSNPEECR
GLFILYKDGD VDSPVVRERI WQNSDFNFDN VLSAMMALFT VSTFEGWPAL LYKAIDSNGE
NIGPIYNHRV EISIFFIIYI IIVAFFMMNI FVGFVIVTFQ EQGEKEYKNC ELDKNQRQCV
EYALKARPLR RYIPKNPYQY KFWYVVNSSP FEYMMFVLIM LNTLCLAMQH YEQSKMFNDA
MDILNMVFTG VFTVEMVLKV IAFKPKGYFS DAWNTFDSLI VIGSIIDVAL SEADNSEESN
RISITFFRLF RVMRLVKLLS RGEGIRTLLW TFIKSFQALP YVALLIAMLF FIYAVIGMQM
FGKVAMRDNN QINRNNNFQT FPQAVLLLFR CATGEAWQEI MLACLPGKLC DPESDYNPGE
EYTCGSNFAI VYFISFYMLC AFLIINLFVA VIMDNFDYLT RDWSILGPHH LDEFKRIWSE
YDPEAKGRIK HLDVVTLLRR IQPPLGFGKL CPHRVACKRL VAMNMPLNSD GTVMFNATLF
ALVRTALKIK TEGNLEQANE ELRAVIKKIW KKTSMKLLDQ VVPPAGDDEV TVGKFYATFL
IQDYFRKFKK RKEQGLVGKY PAKNTTIALQ AGLRTLHDIG PEIRRAISCD LQDDEPEETK
REEEDDVFKR NGALLGNHVN HVNSDRRDSL QQTNTTHRPL HVQRPSIPPA SDTEKPLFPP
AGNSVCHNHH NHNSIGKQVP TSTNANLNNA NMSKAAHGKR PSIGNLEHVS ENGHHSSHKH
DREPQRRSSV KRTRYYETYI RSDSGDEQLP TICREDPEIH GYFRDPHCLG EQEYFSSEEC
YEDDSSPTWS RQNYGYYSRY PGRNIDSERP RGYHHPQGFL EDDDSPVCYD SRRSPRRRLL
PPTPASHRRS SFNFECLRRQ SSQEEVPSSP IFPHRTALPL HLMQQQIMAV AGLDSSKAQK
YSPSHSTRSW ATPPATPPYR DWTPCYTPLI QVEQSEALDQ VNGSLPSLHR SSWYTDEPDI
SYRTFTPASL TVPSSFRNKN SDKQRSADSL VEAVLISEGL GRYARDPKFV SATKHEIADA
CDLTIDEMES AASTLLNGNV RPRANGDVGP LSHRQDYELQ DFGPGYSDEE PDPGRDEEDL
ADEMICITTL *

Mutated AA sequence

MEMNLPTFSS DLIFIKSTMY QEIDARYKGK VISEAETKGY FSLAFGEANY ARGTRLPLSG
EGPTSQPNSS KQTVLSWQAA IDAARQAKAA QTMSTSAPPP VGSLSQRKRQ QYAKSKKQGN
SSNSRPARAL FCLSLNNPIR RACISIVEWK PFDIFILLAI FANCVALAIY IPFPEDDSNS
TNHNLEKVEY AFLIIFTVET FLKIIAYGLL LHPNAYVRNG WNLLDFVIVI VGLFSVILEQ
LTKETEGGNH SSGKSGGFDV KALRAFRVLR PLRLVSGVPS LQVVLNSIIK AMVPLLHIAL
LVLFVIIIYA IIGLELFIGK MHKTCFFADS DIVAEEDPAP CAFSGNGRQC TANGTECRSG
WVGPNGGITN FDNFAFAMLT VFQCITMEGW TDVLYWVNDA IGWEWPWVYF VSLIILGSFF
VLNLVLGVLS GEFSKEREKA KARGDFQKLR EKQQLEEDLK GYLDWITQAE DIDPENEEEG
GEEGKRNTSM PTSETESVNT ENVSGEGENR GCCGSLCQAI SKSKLSRRWR RWNRFNRRRC
RAAVKSVTFY WLVIVLVFLN TLTISSEHYN QPDWLTQIQD IANKVLLALF TCEMLVKMYS
LGLQAYFVSL FNRFDCFVVC GGITETILVE LEIMSPLGIS VFRCVRLLRI FKVTRHWTSL
SNLVASLLNS LKSIASLLLL LFLFIIIFSL LGMQLFGGKF NFDETQTKRS TFDNFPQALL
TVFQILTGED WNAVMYDGIM AYGGPSSSGM IVCIYFIILF ICGNYILLNV FLAIAVDNLA
DAESLNTAQK EEAEEKERKK IARKESLENK KNNKPEVNQI ANSDNKVTID DYREEDEDKD
PYPPCDVPVG EEEEEEEEDE PEVPAGPRPR RISELNMKEK IAPIPEGSAF FILSKTNPIR
VGCHKLINHH IFTNLILVFI MLSSAALAAE DPIRSHSFRN TILGYFDYAF TAIFTVEILL
KMTTFGAFLH KGAFCRNYFN LLDMLVVGVS LVSFGIQSSA ISVVKILRVL RVLRPLRAIN
RAKGLKHVVQ CVFVAIRTIG NIMIVTTLLQ FMFACIGVQL FKGKFYRCTD EAKSNPEECR
GLFILYKDGD VDSPVVRERI WQNSDFNFDN VLSAMMALFT VSTFEGWPAL LYKAIDSNGE
NIGPIYNHRV EISIFFIIYI IIVAFFMMNI FVGFVIVTFQ EQGEKEYKNC ELDKNQRQCV
EYALKARPLR RYIPKNPYQY KFWYVVNSSP FEYMMFVLIM LNTLCLAMQH YEQSKMFNDA
MDILNMVFTG VFTVEMVLKV IAFKPKGYFS DAWNTFDSLI VIGSIIDVAL SEADNSEESN
RISITFFRLF RVMRLVKLLS RGEGIRTLLW TFIKSFQALP YVALLIAMLF FIYAVIGMQM
FGKVAMRDNN QINRNNNFQT FPQAVLLLFR CATGEAWQEI MLACLPGKLC DPESDYNPGE
EYTCGSNFAI VYFISFYMLC AFLIINLFVA VIMDNFDYLT RDWSILGPHH LDEFKRIWSE
YDPEAKGRIK HLDVVTLLRR IQPPLGFGKL CPHRVACKRL VAMNMPLNSD GTVMFNATLF
ALVRTALKIK TEGNLEQANE ELRAVIKKIW KKTSMKLLDQ VVPPAGDDEV TVGKFYATFL
IQDYFRKFKK RKEQGLVGKY PAKNTTIALQ AGLRTLHDIG PEIRRAISCD LQDDEPEETK
REEEDDVFKR NGALLGNHVN HVNSDRRDSL QQTNTTHRPL HVQRPSIPPA SDTEKPLFPP
AGNSVCHNHH NHNSIGKQVP TSTNANLNNA NMSKAAHGKR PSIGNLEHVS ENGHHSSHKH
DREPQRRSSV KRTRYYETYI RSDSGDEQLP TICREDPEIH GYFRDPHCLG EQEYFSSEEC
YEDDSSPTWS RQNYGYYSRY PGRNIDSERP RGYHHPQGFL EDDDSPVCYD SRRSPRRRLL
PPTPASHRRS SFNFECLRRQ SSQEEVPSSP IFPHRTALPL HLMQQQIMAV AGLDSSKAQK
YSPSHSTRSW ATPPATPPYR DWTPCYTPLI QVEQSEALDQ VNGSLPSLHR SSWYTDEPDI
SYRTFTPASL TVPSSFRNKN SDKQRSADSL VEAVLISEGL GRYARDPKFV SATKHEIADA
CDLTIDEMES AASTLLNGNV RPRANGDVGP LSHRQDYELQ DFGPGYSDEE PDPGRDEEDL
ADEMICITTL *

Position of stopcodon in wt / mu CDS

6513 / 6513

Position (AA) of stopcodon in wt / mu AA sequence

2171 / 2171

Position of stopcodon in wt / mu cDNA

6856 / 6856

Position of start ATG in wt / mu cDNA

344 / 344

Last intron/exon boundary

6562

Theoretical NMD boundary in CDS

6168

Length of CDS

6513

Coding sequence (CDS) position

2011

cDNA position

2354

gDNA position

394876

Chromosomal position

53723838

Speed

0.06 s

Back to summary table

Variant:

3:53723838A>T_7_ENST00000636570

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed

Model: simple_aae
Tree vote: 84|16 (del | benign) ?

Analysed issue

Analysis result

Variant

Chr3:53723838A>T (GRCh38)

Gene symbol

CACNA1D

Gene constraints

LOEUF: 0.25, LOF (oe): 0.19, misssense (oe): 0.64, synonymous (oe): 0.91 ? (gnomAD)

Ensembl transcript ID

ENST00000636570.1

Genbank transcript ID

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1939A>T
g.394876A>T

AA changes

AAE:	M647L	?
Score:	15

Frameshift

Length of protein

Normal

Pathogenic variant (ClinVar)

Variant not listed in ClinVar as (likely) pathogenic.

Variant DBs

dbSNP ID	rs368260280
gnomAD	homozygous (T/T)	heterozygous	allele carriers
	0	74	74

Protein conservation

Species	Match	AA	Alignment
Human		647	L	S	N	L	V	A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F	L
mutated	all conserved	647	L	S	N	L	V	A	S	L	L	N	S	L	K	S	I	A	S	L	L	L	L	L	F
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

N/A

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	2.735	1
	6.318	1
(flanking)	8.017	1

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

Strand

Original gDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered gDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Original cDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered cDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Wildtype AA sequence

MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
ITMEGWTDVL YWVNDAIGWE WPWVYFVSLI ILGSFFVLNL VLGVLSGEFS KEREKAKARG
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
GEGENRGCCG SLCQAISKSK LSRRWRRWNR FNRRRCRAAV KSVTFYWLVI VLVFLNTLTI
SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ AYFVSLFNRF DCFVVCGGIT
ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV ASLLNSMKSI ASLLLLLFLF
IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ ILTGEDWNAV MYDGIMAYGG
PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES LNTAQKEEAE EKERKKIARK
ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP CDVPVGEEEE EEEEDEPEVP
AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH KLINHHIFTN LILVFIMLSS
AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT FGAFLHKGAF CRNYFNLLDM
LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG LKHVVQCVFV AIRTIGNIMI
VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI LYKDGDVDSP VVRERIWQNS
DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP IYNHRVEISI FFIIYIIIVA
FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL KARPLRRYIP KNPYQYKFWY
VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL NMVFTGVFTV EMVLKVIAFK
PKGYFSDAWN TFDSLIVIGS IIDVALSEAD NSEESNRISI TFFRLFRVMR LVKLLSRGEG
IRTLLWTFIK SFQALPYVAL LIAMLFFIYA VIGMQMFGKV AMRDNNQINR NNNFQTFPQA
VLLLFRCATG EAWQEIMLAC LPGKLCDPES DYNPGEEYTC GSNFAIVYFI SFYMLCAFLI
INLFVAVIMD NFDYLTRDWS ILGPHHLDEF KRIWSEYDPE AKGRIKHLDV VTLLRRIQPP
LGFGKLCPHR VACKRLVAMN MPLNSDGTVM FNATLFALVR TALKIKTEGN LEQANEELRA
VIKKIWKKTS MKLLDQVVPP AGDDEVTVGK FYATFLIQDY FRKFKKRKEQ GLVGKYPAKN
TTIALQAGLR TLHDIGPEIR RAISCDLQDD EPEETKREEE DDVFKRNGAL LGNHVNHVNS
DRRDSLQQTN TTHRPLHVQR PSIPPASDTE KPLFPPAGNS VCHNHHNHNS IGKQVPTSTN
ANLNNANMSK AAHGKRPSIG NLEHVSENGH HSSHKHDREP QRRSSVKRTR YYETYIRSDS
GDEQLPTICR EDPEIHGYFR DPHCLGEQEY FSSEECYEDD SSPTWSRQNY GYYSRYPGRN
IDSERPRGYH HPQGFLEDDD SPVCYDSRRS PRRRLLPPTP ASHRRSSFNF ECLRRQSSQE
EVPSSPIFPH RTALPLHLMQ QQIMAVAGLD SSKAQKYSPS HSTRSWATPP ATPPYRDWTP
CYTPLIQVEQ SEALDQVNGS LPSLHRSSWY TDEPDISYRT FTPASLTVPS SFRNKNSDKQ
RSADSLVEAV LISEGLGRYA RDPKFVSATK HEIADACDLT IDEMESAAST LLNGNVRPRA
NGDVGPLSHR QDYELQDFGP GYSDEEPDPG RDEEDLADEM ICITTL*

Mutated AA sequence

MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
ITMEGWTDVL YWVNDAIGWE WPWVYFVSLI ILGSFFVLNL VLGVLSGEFS KEREKAKARG
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
GEGENRGCCG SLCQAISKSK LSRRWRRWNR FNRRRCRAAV KSVTFYWLVI VLVFLNTLTI
SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ AYFVSLFNRF DCFVVCGGIT
ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV ASLLNSLKSI ASLLLLLFLF
IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ ILTGEDWNAV MYDGIMAYGG
PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES LNTAQKEEAE EKERKKIARK
ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP CDVPVGEEEE EEEEDEPEVP
AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH KLINHHIFTN LILVFIMLSS
AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT FGAFLHKGAF CRNYFNLLDM
LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG LKHVVQCVFV AIRTIGNIMI
VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI LYKDGDVDSP VVRERIWQNS
DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP IYNHRVEISI FFIIYIIIVA
FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL KARPLRRYIP KNPYQYKFWY
VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL NMVFTGVFTV EMVLKVIAFK
PKGYFSDAWN TFDSLIVIGS IIDVALSEAD NSEESNRISI TFFRLFRVMR LVKLLSRGEG
IRTLLWTFIK SFQALPYVAL LIAMLFFIYA VIGMQMFGKV AMRDNNQINR NNNFQTFPQA
VLLLFRCATG EAWQEIMLAC LPGKLCDPES DYNPGEEYTC GSNFAIVYFI SFYMLCAFLI
INLFVAVIMD NFDYLTRDWS ILGPHHLDEF KRIWSEYDPE AKGRIKHLDV VTLLRRIQPP
LGFGKLCPHR VACKRLVAMN MPLNSDGTVM FNATLFALVR TALKIKTEGN LEQANEELRA
VIKKIWKKTS MKLLDQVVPP AGDDEVTVGK FYATFLIQDY FRKFKKRKEQ GLVGKYPAKN
TTIALQAGLR TLHDIGPEIR RAISCDLQDD EPEETKREEE DDVFKRNGAL LGNHVNHVNS
DRRDSLQQTN TTHRPLHVQR PSIPPASDTE KPLFPPAGNS VCHNHHNHNS IGKQVPTSTN
ANLNNANMSK AAHGKRPSIG NLEHVSENGH HSSHKHDREP QRRSSVKRTR YYETYIRSDS
GDEQLPTICR EDPEIHGYFR DPHCLGEQEY FSSEECYEDD SSPTWSRQNY GYYSRYPGRN
IDSERPRGYH HPQGFLEDDD SPVCYDSRRS PRRRLLPPTP ASHRRSSFNF ECLRRQSSQE
EVPSSPIFPH RTALPLHLMQ QQIMAVAGLD SSKAQKYSPS HSTRSWATPP ATPPYRDWTP
CYTPLIQVEQ SEALDQVNGS LPSLHRSSWY TDEPDISYRT FTPASLTVPS SFRNKNSDKQ
RSADSLVEAV LISEGLGRYA RDPKFVSATK HEIADACDLT IDEMESAAST LLNGNVRPRA
NGDVGPLSHR QDYELQDFGP GYSDEEPDPG RDEEDLADEM ICITTL*

Position of stopcodon in wt / mu CDS

6441 / 6441

Position (AA) of stopcodon in wt / mu AA sequence

2147 / 2147

Position of stopcodon in wt / mu cDNA

6441 / 6441

Position of start ATG in wt / mu cDNA

1 / 1

Last intron/exon boundary

6147

Theoretical NMD boundary in CDS

6096

Length of CDS

6441

Coding sequence (CDS) position

1939

cDNA position

1939

gDNA position

394876

Chromosomal position

53723838

Speed

0.05 s

Back to summary table

Variant:

3:53723838A>T_8_ENST00000422281

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Protein features (might be) affected

Model: simple_aae
Tree vote: 84|16 (del | benign) ?

Analysed issue

Analysis result

Variant

Chr3:53723838A>T (GRCh38)

Gene symbol

CACNA1D

Gene constraints

LOEUF: 0.25, LOF (oe): 0.19, misssense (oe): 0.64, synonymous (oe): 0.92 ? (gnomAD)

Ensembl transcript ID

ENST00000422281.7

Genbank transcript ID

NM_001128839 (by similarity)

UniProt / AlphaMissense peptide

CAC1D_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1939A>T
g.394876A>T

AA changes

AAE:	M647L	?
Score:	15

Frameshift

Length of protein

Normal

Pathogenic variant (ClinVar)

Variant not listed in ClinVar as (likely) pathogenic.

Variant DBs

dbSNP ID	rs368260280
gnomAD	homozygous (T/T)	heterozygous	allele carriers
	0	74	74

Protein conservation

Species	Match	AA	Alignment
Human		647	L	S	N	L	V	A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F	L
mutated	all conserved	647	L	S	N	L	V	A	S	L	L	N	S	L	K	S	I	A	S	L	L	L	L	L	F
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

Start (aa)	End (aa)	Feature	Details
1	2161	CHAIN		lost
509	755	REPEAT	II	lost
634	652	TOPO_DOM	Cytoplasmic	lost
647	672	HELIX		lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	2.735	1
	6.318	1
(flanking)	8.017	1

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

Strand

Original gDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered gDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Original cDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered cDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Wildtype AA sequence

MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
ITMEGWTDVL YWMNDAMGFE LPWVYFVSLV IFGSFFVLNL VLGVLSGEFS KEREKAKARG
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
GEGENRGCCG SLCQAISKSK LSRRWRRWNR FNRRRCRAAV KSVTFYWLVI VLVFLNTLTI
SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ AYFVSLFNRF DCFVVCGGIT
ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV ASLLNSMKSI ASLLLLLFLF
IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ ILTGEDWNAV MYDGIMAYGG
PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES LNTAQKEEAE EKERKKIARK
ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP CDVPVGEEEE EEEEDEPEVP
AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH KLINHHIFTN LILVFIMLSS
AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT FGAFLHKGAF CRNYFNLLDM
LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG LKHVVQCVFV AIRTIGNIMI
VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI LYKDGDVDSP VVRERIWQNS
DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP IYNHRVEISI FFIIYIIIVA
FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL KARPLRRYIP KNPYQYKFWY
VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL NMVFTGVFTV EMVLKVIAFK
PKGYFSDAWN TFDSLIVIGS IIDVALSEAD NSEESNRISI TFFRLFRVMR LVKLLSRGEG
IRTLLWTFIK SFQALPYVAL LIAMLFFIYA VIGMQMFGKV AMRDNNQINR NNNFQTFPQA
VLLLFRCATG EAWQEIMLAC LPGKLCDPES DYNPGEEYTC GSNFAIVYFI SFYMLCAFLI
INLFVAVIMD NFDYLTRDWS ILGPHHLDEF KRIWSEYDPE AKGRIKHLDV VTLLRRIQPP
LGFGKLCPHR VACKRLVAMN MPLNSDGTVM FNATLFALVR TALKIKTEGN LEQANEELRA
VIKKIWKKTS MKLLDQVVPP AGDDEVTVGK FYATFLIQDY FRKFKKRKEQ GLVGKYPAKN
TTIALQAGLR TLHDIGPEIR RAISCDLQDD EPEETKREEE DDVFKRNGAL LGNHVNHVNS
DRRDSLQQTN TTHRPLHVQR PSIPPASDTE KPLFPPAGNS VCHNHHNHNS IGKQVPTSTN
ANLNNANMSK AAHGKRPSIG NLEHVSENGH HSSHKHDREP QRRSSVKRSD SGDEQLPTIC
REDPEIHGYF RDPHCLGEQE YFSSEECYED DSSPTWSRQN YGYYSRYPGR NIDSERPRGY
HHPQGFLEDD DSPVCYDSRR SPRRRLLPPT PASHRRSSFN FECLRRQSSQ EEVPSSPIFP
HRTALPLHLM QQQIMAVAGL DSSKAQKYSP SHSTRSWATP PATPPYRDWT PCYTPLIQVE
QSEALDQVNG SLPSLHRSSW YTDEPDISYR TFTPASLTVP SSFRNKNSDK QRSADSLVEA
VLISEGLGRY ARDPKFVSAT KHEIADACDL TIDEMESAAS TLLNGNVRPR ANGDVGPLSH
RQDYELQDFG PGYSDEEPDP GRDEEDLADE MICITTL*

Mutated AA sequence

MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
ITMEGWTDVL YWMNDAMGFE LPWVYFVSLV IFGSFFVLNL VLGVLSGEFS KEREKAKARG
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
GEGENRGCCG SLCQAISKSK LSRRWRRWNR FNRRRCRAAV KSVTFYWLVI VLVFLNTLTI
SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ AYFVSLFNRF DCFVVCGGIT
ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV ASLLNSLKSI ASLLLLLFLF
IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ ILTGEDWNAV MYDGIMAYGG
PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES LNTAQKEEAE EKERKKIARK
ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP CDVPVGEEEE EEEEDEPEVP
AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH KLINHHIFTN LILVFIMLSS
AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT FGAFLHKGAF CRNYFNLLDM
LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG LKHVVQCVFV AIRTIGNIMI
VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI LYKDGDVDSP VVRERIWQNS
DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP IYNHRVEISI FFIIYIIIVA
FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL KARPLRRYIP KNPYQYKFWY
VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL NMVFTGVFTV EMVLKVIAFK
PKGYFSDAWN TFDSLIVIGS IIDVALSEAD NSEESNRISI TFFRLFRVMR LVKLLSRGEG
IRTLLWTFIK SFQALPYVAL LIAMLFFIYA VIGMQMFGKV AMRDNNQINR NNNFQTFPQA
VLLLFRCATG EAWQEIMLAC LPGKLCDPES DYNPGEEYTC GSNFAIVYFI SFYMLCAFLI
INLFVAVIMD NFDYLTRDWS ILGPHHLDEF KRIWSEYDPE AKGRIKHLDV VTLLRRIQPP
LGFGKLCPHR VACKRLVAMN MPLNSDGTVM FNATLFALVR TALKIKTEGN LEQANEELRA
VIKKIWKKTS MKLLDQVVPP AGDDEVTVGK FYATFLIQDY FRKFKKRKEQ GLVGKYPAKN
TTIALQAGLR TLHDIGPEIR RAISCDLQDD EPEETKREEE DDVFKRNGAL LGNHVNHVNS
DRRDSLQQTN TTHRPLHVQR PSIPPASDTE KPLFPPAGNS VCHNHHNHNS IGKQVPTSTN
ANLNNANMSK AAHGKRPSIG NLEHVSENGH HSSHKHDREP QRRSSVKRSD SGDEQLPTIC
REDPEIHGYF RDPHCLGEQE YFSSEECYED DSSPTWSRQN YGYYSRYPGR NIDSERPRGY
HHPQGFLEDD DSPVCYDSRR SPRRRLLPPT PASHRRSSFN FECLRRQSSQ EEVPSSPIFP
HRTALPLHLM QQQIMAVAGL DSSKAQKYSP SHSTRSWATP PATPPYRDWT PCYTPLIQVE
QSEALDQVNG SLPSLHRSSW YTDEPDISYR TFTPASLTVP SSFRNKNSDK QRSADSLVEA
VLISEGLGRY ARDPKFVSAT KHEIADACDL TIDEMESAAS TLLNGNVRPR ANGDVGPLSH
RQDYELQDFG PGYSDEEPDP GRDEEDLADE MICITTL*

Position of stopcodon in wt / mu CDS

6414 / 6414

Position (AA) of stopcodon in wt / mu AA sequence

2138 / 2138

Position of stopcodon in wt / mu cDNA

6414 / 6414

Position of start ATG in wt / mu cDNA

1 / 1

Last intron/exon boundary

6120

Theoretical NMD boundary in CDS

6069

Length of CDS

6414

Coding sequence (CDS) position

1939

cDNA position

1939

gDNA position

394876

Chromosomal position

53723838

Speed

0.05 s

Back to summary table

Variant:

3:53723838A>T_3_ENST00000481478

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed

Model: simple_aae
Tree vote: 87|13 (del | benign) ?

Analysed issue

Analysis result

Variant

Chr3:53723838A>T (GRCh38)

Gene symbol

CACNA1D

Gene constraints

LOEUF: 0.27, LOF (oe): 0.21, misssense (oe): 0.66, synonymous (oe): 0.91 ? (gnomAD)

Ensembl transcript ID

ENST00000481478.2

Genbank transcript ID

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1999A>T
g.394876A>T

AA changes

AAE:	M667L	?
Score:	15

Frameshift

Length of protein

Normal

Pathogenic variant (ClinVar)

Variant not listed in ClinVar as (likely) pathogenic.

Variant DBs

dbSNP ID	rs368260280
gnomAD	homozygous (T/T)	heterozygous	allele carriers
	0	74	74

Protein conservation

Species	Match	AA	Alignment
Human		667	L	S	N	L	V	A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F	L
mutated	all conserved	667						A	S	L	L	N	S	L	K	S	I	A	S	L	L	L	L	L	F
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

N/A

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	2.735	1
	6.318	1
(flanking)	8.017	1

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

Strand

Original gDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered gDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Original cDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered cDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Wildtype AA sequence

MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
ITMEGWTDVL YWMNDAMGFE LPWVYFVSLV IFGSFFVLNL VLGVLSGEFS KEREKAKARG
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
GEGENRGCCG SLWCWWRRRG AAKAGPSGCR RWGQAISKSK LSRRWRRWNR FNRRRCRAAV
KSVTFYWLVI VLVFLNTLTI SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ
AYFVSLFNRF DCFVVCGGIT ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV
ASLLNSMKSI ASLLLLLFLF IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ
ILTGEDWNAV MYDGIMAYGG PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES
LNTAQKEEAE EKERKKIARK ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP
CDVPVGEEEE EEEEDEPEVP AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH
KLINHHIFTN LILVFIMLSS AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT
FGAFLHKGAF CRNYFNLLDM LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG
LKHVVQCVFV AIRTIGNIMI VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI
LYKDGDVDSP VVRERIWQNS DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP
IYNHRVEISI FFIIYIIIVA FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL
KARPLRRYIP KNPYQYKFWY VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL
NMVFTGVFTV EMVLKVIAFK PKHYFTDAWN TFDALIVVGS VVDIAITEVN PTESENVPVP
TATPGNSEES NRISITFFRL FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL PYVALLIAML
FFIYAVIGMQ MFGKVAMRDN NQINRNNNFQ TFPQAVLLLF RCATGEAWQE IMLACLPGKL
CDPESDYNPG EEYTCGSNFA IVYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH
HLDEFKRIWS EYDPEAKGRI KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVAMNMPLNS
DGTVMFNATL FALVRTALKI KTEGNLEQAN EELRAVIKKI WKKTSMKLLD QVVPPAGDDE
VTVGKFYATF LIQDYFRKFK KRKEQGLVGK YPAKNTTIAL QAGLRTLHDI GPEIRRAISC
DLQDDEPEET KREEEDDVFK RNGALLGNHV NHVNSDRRDS LQQTNTTHRP LHVQRPSIPP
ASDTEKPLFP PAGNSVCHNH HNHNSIGKQV PTSTNANLNN ANMSKAAHGK RPSIGNLEHV
SENGHHSSHK HDREPQRRSS VKRTRYYETY IRSDSGDEQL PTICREDPEI HGYFRDPHCL
GEQEYFSSEE CYEDDSSPTW SRQNYGYYSR YPGRNIDSER PRGYHHPQGF LEDDDSPVCY
DSRRSPRRRL LPPTPASHRR SSFNFECLRR QSSQEEVPSS PIFPHRTALP LHLMQQQIMA
VAGLDSSKAQ KYSPSHSTRS WATPPATPPY RDWTPCYTPL IQVEQSEALD QVNGSLPSLH
RSSWYTDEPD ISYRTFTPAS LTVPSSFRNK NSDKQRSADS LVEAVLISEG LGRYARDPKF
VSATKHEIAD ACDLTIDEME SAASTLLNGN VRPRANGDVG PLSHRQDYEL QDFGPGYSDE
EPDPGRDEED LADEMICITT L*

Mutated AA sequence

MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
ITMEGWTDVL YWMNDAMGFE LPWVYFVSLV IFGSFFVLNL VLGVLSGEFS KEREKAKARG
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
GEGENRGCCG SLWCWWRRRG AAKAGPSGCR RWGQAISKSK LSRRWRRWNR FNRRRCRAAV
KSVTFYWLVI VLVFLNTLTI SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ
AYFVSLFNRF DCFVVCGGIT ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV
ASLLNSLKSI ASLLLLLFLF IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ
ILTGEDWNAV MYDGIMAYGG PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES
LNTAQKEEAE EKERKKIARK ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP
CDVPVGEEEE EEEEDEPEVP AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH
KLINHHIFTN LILVFIMLSS AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT
FGAFLHKGAF CRNYFNLLDM LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG
LKHVVQCVFV AIRTIGNIMI VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI
LYKDGDVDSP VVRERIWQNS DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP
IYNHRVEISI FFIIYIIIVA FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL
KARPLRRYIP KNPYQYKFWY VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL
NMVFTGVFTV EMVLKVIAFK PKHYFTDAWN TFDALIVVGS VVDIAITEVN PTESENVPVP
TATPGNSEES NRISITFFRL FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL PYVALLIAML
FFIYAVIGMQ MFGKVAMRDN NQINRNNNFQ TFPQAVLLLF RCATGEAWQE IMLACLPGKL
CDPESDYNPG EEYTCGSNFA IVYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH
HLDEFKRIWS EYDPEAKGRI KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVAMNMPLNS
DGTVMFNATL FALVRTALKI KTEGNLEQAN EELRAVIKKI WKKTSMKLLD QVVPPAGDDE
VTVGKFYATF LIQDYFRKFK KRKEQGLVGK YPAKNTTIAL QAGLRTLHDI GPEIRRAISC
DLQDDEPEET KREEEDDVFK RNGALLGNHV NHVNSDRRDS LQQTNTTHRP LHVQRPSIPP
ASDTEKPLFP PAGNSVCHNH HNHNSIGKQV PTSTNANLNN ANMSKAAHGK RPSIGNLEHV
SENGHHSSHK HDREPQRRSS VKRTRYYETY IRSDSGDEQL PTICREDPEI HGYFRDPHCL
GEQEYFSSEE CYEDDSSPTW SRQNYGYYSR YPGRNIDSER PRGYHHPQGF LEDDDSPVCY
DSRRSPRRRL LPPTPASHRR SSFNFECLRR QSSQEEVPSS PIFPHRTALP LHLMQQQIMA
VAGLDSSKAQ KYSPSHSTRS WATPPATPPY RDWTPCYTPL IQVEQSEALD QVNGSLPSLH
RSSWYTDEPD ISYRTFTPAS LTVPSSFRNK NSDKQRSADS LVEAVLISEG LGRYARDPKF
VSATKHEIAD ACDLTIDEME SAASTLLNGN VRPRANGDVG PLSHRQDYEL QDFGPGYSDE
EPDPGRDEED LADEMICITT L*

Position of stopcodon in wt / mu CDS

6546 / 6546

Position (AA) of stopcodon in wt / mu AA sequence

2182 / 2182

Position of stopcodon in wt / mu cDNA

7102 / 7102

Position of start ATG in wt / mu cDNA

557 / 557

Last intron/exon boundary

6808

Theoretical NMD boundary in CDS

6201

Length of CDS

6546

Coding sequence (CDS) position

1999

cDNA position

2555

gDNA position

394876

Chromosomal position

53723838

Speed

0.05 s

Back to summary table

Variant:

3:53723838A>T_4_ENST00000288139

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Protein features (might be) affected

Model: simple_aae
Tree vote: 87|13 (del | benign) ?

Analysed issue

Analysis result

Variant

Chr3:53723838A>T (GRCh38)

Gene symbol

CACNA1D

Gene constraints

LOEUF: 0.26, LOF (oe): 0.20, misssense (oe): 0.65, synonymous (oe): 0.92 ? (gnomAD)

Ensembl transcript ID

ENST00000288139.11

Genbank transcript ID

NM_000720 (exact from MANE)

UniProt / AlphaMissense peptide

CAC1D_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1999A>T
g.394876A>T

AA changes

AAE:	M667L	?
Score:	15

Frameshift

Length of protein

Normal

Pathogenic variant (ClinVar)

Variant not listed in ClinVar as (likely) pathogenic.

Variant DBs

dbSNP ID	rs368260280
gnomAD	homozygous (T/T)	heterozygous	allele carriers
	0	74	74

Protein conservation

Species	Match	AA	Alignment
Human		667	L	S	N	L	V	A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F	L
mutated	all conserved	667						A	S	L	L	N	S	L	K	S	I	A	S	L	L	L	L	L	F
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

Start (aa)	End (aa)	Feature	Details
1	2161	CHAIN		lost
509	755	REPEAT	II	lost
647	672	HELIX		lost
653	673	TRANSMEM	Helical	lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	2.735	1
	6.318	1
(flanking)	8.017	1

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

Strand

Original gDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered gDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Original cDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered cDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Wildtype AA sequence

MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
ITMEGWTDVL YWVNDAIGWE WPWVYFVSLI ILGSFFVLNL VLGVLSGEFS KEREKAKARG
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
GEGENRGCCG SLWCWWRRRG AAKAGPSGCR RWGQAISKSK LSRRWRRWNR FNRRRCRAAV
KSVTFYWLVI VLVFLNTLTI SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ
AYFVSLFNRF DCFVVCGGIT ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV
ASLLNSMKSI ASLLLLLFLF IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ
ILTGEDWNAV MYDGIMAYGG PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES
LNTAQKEEAE EKERKKIARK ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP
CDVPVGEEEE EEEEDEPEVP AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH
KLINHHIFTN LILVFIMLSS AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT
FGAFLHKGAF CRNYFNLLDM LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG
LKHVVQCVFV AIRTIGNIMI VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI
LYKDGDVDSP VVRERIWQNS DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP
IYNHRVEISI FFIIYIIIVA FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL
KARPLRRYIP KNPYQYKFWY VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL
NMVFTGVFTV EMVLKVIAFK PKGYFSDAWN TFDSLIVIGS IIDVALSEAD PTESENVPVP
TATPGNSEES NRISITFFRL FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL PYVALLIAML
FFIYAVIGMQ MFGKVAMRDN NQINRNNNFQ TFPQAVLLLF RCATGEAWQE IMLACLPGKL
CDPESDYNPG EEYTCGSNFA IVYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH
HLDEFKRIWS EYDPEAKGRI KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVAMNMPLNS
DGTVMFNATL FALVRTALKI KTEGNLEQAN EELRAVIKKI WKKTSMKLLD QVVPPAGDDE
VTVGKFYATF LIQDYFRKFK KRKEQGLVGK YPAKNTTIAL QAGLRTLHDI GPEIRRAISC
DLQDDEPEET KREEEDDVFK RNGALLGNHV NHVNSDRRDS LQQTNTTHRP LHVQRPSIPP
ASDTEKPLFP PAGNSVCHNH HNHNSIGKQV PTSTNANLNN ANMSKAAHGK RPSIGNLEHV
SENGHHSSHK HDREPQRRSS VKRTRYYETY IRSDSGDEQL PTICREDPEI HGYFRDPHCL
GEQEYFSSEE CYEDDSSPTW SRQNYGYYSR YPGRNIDSER PRGYHHPQGF LEDDDSPVCY
DSRRSPRRRL LPPTPASHRR SSFNFECLRR QSSQEEVPSS PIFPHRTALP LHLMQQQIMA
VAGLDSSKAQ KYSPSHSTRS WATPPATPPY RDWTPCYTPL IQVEQSEALD QVNGSLPSLH
RSSWYTDEPD ISYRTFTPAS LTVPSSFRNK NSDKQRSADS LVEAVLISEG LGRYARDPKF
VSATKHEIAD ACDLTIDEME SAASTLLNGN VRPRANGDVG PLSHRQDYEL QDFGPGYSDE
EPDPGRDEED LADEMICITT L*

Mutated AA sequence

MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
ITMEGWTDVL YWVNDAIGWE WPWVYFVSLI ILGSFFVLNL VLGVLSGEFS KEREKAKARG
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
GEGENRGCCG SLWCWWRRRG AAKAGPSGCR RWGQAISKSK LSRRWRRWNR FNRRRCRAAV
KSVTFYWLVI VLVFLNTLTI SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ
AYFVSLFNRF DCFVVCGGIT ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV
ASLLNSLKSI ASLLLLLFLF IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ
ILTGEDWNAV MYDGIMAYGG PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES
LNTAQKEEAE EKERKKIARK ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP
CDVPVGEEEE EEEEDEPEVP AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH
KLINHHIFTN LILVFIMLSS AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT
FGAFLHKGAF CRNYFNLLDM LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG
LKHVVQCVFV AIRTIGNIMI VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI
LYKDGDVDSP VVRERIWQNS DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP
IYNHRVEISI FFIIYIIIVA FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL
KARPLRRYIP KNPYQYKFWY VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL
NMVFTGVFTV EMVLKVIAFK PKGYFSDAWN TFDSLIVIGS IIDVALSEAD PTESENVPVP
TATPGNSEES NRISITFFRL FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL PYVALLIAML
FFIYAVIGMQ MFGKVAMRDN NQINRNNNFQ TFPQAVLLLF RCATGEAWQE IMLACLPGKL
CDPESDYNPG EEYTCGSNFA IVYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH
HLDEFKRIWS EYDPEAKGRI KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVAMNMPLNS
DGTVMFNATL FALVRTALKI KTEGNLEQAN EELRAVIKKI WKKTSMKLLD QVVPPAGDDE
VTVGKFYATF LIQDYFRKFK KRKEQGLVGK YPAKNTTIAL QAGLRTLHDI GPEIRRAISC
DLQDDEPEET KREEEDDVFK RNGALLGNHV NHVNSDRRDS LQQTNTTHRP LHVQRPSIPP
ASDTEKPLFP PAGNSVCHNH HNHNSIGKQV PTSTNANLNN ANMSKAAHGK RPSIGNLEHV
SENGHHSSHK HDREPQRRSS VKRTRYYETY IRSDSGDEQL PTICREDPEI HGYFRDPHCL
GEQEYFSSEE CYEDDSSPTW SRQNYGYYSR YPGRNIDSER PRGYHHPQGF LEDDDSPVCY
DSRRSPRRRL LPPTPASHRR SSFNFECLRR QSSQEEVPSS PIFPHRTALP LHLMQQQIMA
VAGLDSSKAQ KYSPSHSTRS WATPPATPPY RDWTPCYTPL IQVEQSEALD QVNGSLPSLH
RSSWYTDEPD ISYRTFTPAS LTVPSSFRNK NSDKQRSADS LVEAVLISEG LGRYARDPKF
VSATKHEIAD ACDLTIDEME SAASTLLNGN VRPRANGDVG PLSHRQDYEL QDFGPGYSDE
EPDPGRDEED LADEMICITT L*

Position of stopcodon in wt / mu CDS

6546 / 6546

Position (AA) of stopcodon in wt / mu AA sequence

2182 / 2182

Position of stopcodon in wt / mu cDNA

7102 / 7102

Position of start ATG in wt / mu cDNA

557 / 557

Last intron/exon boundary

6808

Theoretical NMD boundary in CDS

6201

Length of CDS

6546

Coding sequence (CDS) position

1999

cDNA position

2555

gDNA position

394876

Chromosomal position

53723838

Speed

0.05 s

Back to summary table

Variant:

3:53723838A>T_9_ENST00000640483

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed

Model: simple_aae
Tree vote: 90|10 (del | benign) ?

Analysed issue

Analysis result

Variant

Chr3:53723838A>T (GRCh38)

Gene symbol

CACNA1D

Gene constraints

LOEUF: 0.29, LOF (oe): 0.22, misssense (oe): 0.59, synonymous (oe): 0.93 ? (gnomAD)

Ensembl transcript ID

ENST00000640483.1

Genbank transcript ID

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1972A>T
g.394876A>T

AA changes

AAE:	M658L	?
Score:	15

Frameshift

Length of protein

Normal

Pathogenic variant (ClinVar)

Variant not listed in ClinVar as (likely) pathogenic.

Variant DBs

dbSNP ID	rs368260280
gnomAD	homozygous (T/T)	heterozygous	allele carriers
	0	74	74

Protein conservation

Species	Match	AA	Alignment
Human		658	L	S	N	L	V	A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F	L
mutated	all conserved	658	L	S	N	L	V	A	S	L	L	N	S	L	K	S
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

N/A

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	2.735	1
	6.318	1
(flanking)	8.017	1

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

Strand

Original gDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered gDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Original cDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered cDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Wildtype AA sequence

MQHQRQQQAD HANEANYARG TRLPLSGEGP TSQPNSSKQT VLSWQAAIDA ARQAKAAQTM
STSAPPPVGS LSQRKRQQYA KSKKQGNSSN SRPARALFCL SLNNPIRRAC ISIVEWKPFD
IFILLAIFAN CVALAIYIPF PEDDSNSTNH NLEKVEYAFL IIFTVETFLK IIAYGLLLHP
NAYVRNGWNL LDFVIVIVGL FSVILEQLTK ETEGGNHSSG KSGGFDVKAL RAFRVLRPLR
LVSGVPSLQV VLNSIIKAMV PLLHIALLVL FVIIIYAIIG LELFIGKMHK TCFFADSDIV
AEEDPAPCAF SGNGRQCTAN GTECRSGWVG PNGGITNFDN FAFAMLTVFQ CITMEGWTDV
LYWVNDAIGW EWPWVYFVSL IILGSFFVLN LVLGVLSGEF SKEREKAKAR GDFQKLREKQ
QLEEDLKGYL DWITQAEDID PENEEEGGEE GKRNTSMPTS ETESVNTENV SGEGENRGCC
GSLWCWWRRR GAAKAGPSGC RRWGQAISKS KLSRRWRRWN RFNRRRCRAA VKSVTFYWLV
IVLVFLNTLT ISSEHYNQPD WLTQIQDIAN KVLLALFTCE MLVKMYSLGL QAYFVSLFNR
FDCFVVCGGI TETILVELEI MSPLGISVFR CVRLLRIFKV TRHWTSLSNL VASLLNSMKS
IASLLLLLFL FIIIFSLLGM QLFGGKFNFD ETQTKRSTFD NFPQALLTVF QILTGEDWNA
VMYDGIMAYG GPSSSGMIVC IYFIILFICG NYILLNVFLA IAVDNLADAE SLNTAQKEEA
EEKERKKIAR KESLENKKNN KPEVNQIANS DNKVTIDDYR EEDEDKDPYP PCDVPVGEEE
EEEEEDEPEV PAGPRPRRIS ELNMKEKIAP IPEGSAFFIL SKTNPIRVGC HKLINHHIFT
NLILVFIMLS SAALAAEDPI RSHSFRNTIL GYFDYAFTAI FTVEILLKMT TFGAFLHKGA
FCRNYFNLLD MLVVGVSLVS FGIQSSAISV VKILRVLRVL RPLRAINRAK GLKHVVQCVF
VAIRTIGNIM IVTTLLQFMF ACIGVQLFKG KFYRCTDEAK SNPEECRGLF ILYKDGDVDS
PVVRERIWQN SDFNFDNVLS AMMALFTVST FEGWPALLYK AIDSNGENIG PIYNHRVEIS
IFFIIYIIIV AFFMMNIFVG FVIVTFQEQG EKEYKNCELD KNQRQCVEYA LKARPLRRYI
PKNPYQYKFW YVVNSSPFEY MMFVLIMLNT LCLAMQHYEQ SKMFNDAMDI LNMVFTGVFT
VEMVLKVIAF KPKHYFTDAW NTFDALIVVG SVVDIAITEV NNSEESNRIS ITFFRLFRVM
RLVKLLSRGE GIRTLLWTFI KSFQALPYVA LLIAMLFFIY AVIGMQMFGK VAMRDNNQIN
RNNNFQTFPQ AVLLLFRCAT GEAWQEIMLA CLPGKLCDPE SDYNPGEEYT CGSNFAIVYF
ISFYMLCAFL IINLFVAVIM DNFDYLTRDW SILGPHHLDE FKRIWSEYDP EAKGRIKHLD
VVTLLRRIQP PLGFGKLCPH RVACKRLVAM NMPLNSDGTV MFNATLFALV RTALKIKTEG
NLEQANEELR AVIKKIWKKT SMKLLDQVVP PAGDDEVTVG KFYATFLIQD YFRKFKKRKE
QGLVGKYPAK NTTIALQMLE RML*

Mutated AA sequence

MQHQRQQQAD HANEANYARG TRLPLSGEGP TSQPNSSKQT VLSWQAAIDA ARQAKAAQTM
STSAPPPVGS LSQRKRQQYA KSKKQGNSSN SRPARALFCL SLNNPIRRAC ISIVEWKPFD
IFILLAIFAN CVALAIYIPF PEDDSNSTNH NLEKVEYAFL IIFTVETFLK IIAYGLLLHP
NAYVRNGWNL LDFVIVIVGL FSVILEQLTK ETEGGNHSSG KSGGFDVKAL RAFRVLRPLR
LVSGVPSLQV VLNSIIKAMV PLLHIALLVL FVIIIYAIIG LELFIGKMHK TCFFADSDIV
AEEDPAPCAF SGNGRQCTAN GTECRSGWVG PNGGITNFDN FAFAMLTVFQ CITMEGWTDV
LYWVNDAIGW EWPWVYFVSL IILGSFFVLN LVLGVLSGEF SKEREKAKAR GDFQKLREKQ
QLEEDLKGYL DWITQAEDID PENEEEGGEE GKRNTSMPTS ETESVNTENV SGEGENRGCC
GSLWCWWRRR GAAKAGPSGC RRWGQAISKS KLSRRWRRWN RFNRRRCRAA VKSVTFYWLV
IVLVFLNTLT ISSEHYNQPD WLTQIQDIAN KVLLALFTCE MLVKMYSLGL QAYFVSLFNR
FDCFVVCGGI TETILVELEI MSPLGISVFR CVRLLRIFKV TRHWTSLSNL VASLLNSLKS
IASLLLLLFL FIIIFSLLGM QLFGGKFNFD ETQTKRSTFD NFPQALLTVF QILTGEDWNA
VMYDGIMAYG GPSSSGMIVC IYFIILFICG NYILLNVFLA IAVDNLADAE SLNTAQKEEA
EEKERKKIAR KESLENKKNN KPEVNQIANS DNKVTIDDYR EEDEDKDPYP PCDVPVGEEE
EEEEEDEPEV PAGPRPRRIS ELNMKEKIAP IPEGSAFFIL SKTNPIRVGC HKLINHHIFT
NLILVFIMLS SAALAAEDPI RSHSFRNTIL GYFDYAFTAI FTVEILLKMT TFGAFLHKGA
FCRNYFNLLD MLVVGVSLVS FGIQSSAISV VKILRVLRVL RPLRAINRAK GLKHVVQCVF
VAIRTIGNIM IVTTLLQFMF ACIGVQLFKG KFYRCTDEAK SNPEECRGLF ILYKDGDVDS
PVVRERIWQN SDFNFDNVLS AMMALFTVST FEGWPALLYK AIDSNGENIG PIYNHRVEIS
IFFIIYIIIV AFFMMNIFVG FVIVTFQEQG EKEYKNCELD KNQRQCVEYA LKARPLRRYI
PKNPYQYKFW YVVNSSPFEY MMFVLIMLNT LCLAMQHYEQ SKMFNDAMDI LNMVFTGVFT
VEMVLKVIAF KPKHYFTDAW NTFDALIVVG SVVDIAITEV NNSEESNRIS ITFFRLFRVM
RLVKLLSRGE GIRTLLWTFI KSFQALPYVA LLIAMLFFIY AVIGMQMFGK VAMRDNNQIN
RNNNFQTFPQ AVLLLFRCAT GEAWQEIMLA CLPGKLCDPE SDYNPGEEYT CGSNFAIVYF
ISFYMLCAFL IINLFVAVIM DNFDYLTRDW SILGPHHLDE FKRIWSEYDP EAKGRIKHLD
VVTLLRRIQP PLGFGKLCPH RVACKRLVAM NMPLNSDGTV MFNATLFALV RTALKIKTEG
NLEQANEELR AVIKKIWKKT SMKLLDQVVP PAGDDEVTVG KFYATFLIQD YFRKFKKRKE
QGLVGKYPAK NTTIALQMLE RML*

Position of stopcodon in wt / mu CDS

4932 / 4932

Position (AA) of stopcodon in wt / mu AA sequence

1644 / 1644

Position of stopcodon in wt / mu cDNA

4932 / 4932

Position of start ATG in wt / mu cDNA

1 / 1

Last intron/exon boundary

4911

Theoretical NMD boundary in CDS

4860

Length of CDS

4932

Coding sequence (CDS) position

1972

cDNA position

1972

gDNA position

394876

Chromosomal position

53723838

Speed

0.05 s

Back to summary table

Variant:

3:53723838A>T_2_ENST00000636627

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed

Model: simple_aae
Tree vote: 91|9 (del | benign) ?

Analysed issue

Analysis result

Variant

Chr3:53723838A>T (GRCh38)

Gene symbol

CACNA1D

Gene constraints

LOEUF: 0.32, LOF (oe): 0.23, misssense (oe): 0.58, synonymous (oe): 0.92 ? (gnomAD)

Ensembl transcript ID

ENST00000636627.2

Genbank transcript ID

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1999A>T
g.394876A>T

AA changes

AAE:	M667L	?
Score:	15

Frameshift

Length of protein

Normal

Pathogenic variant (ClinVar)

Variant not listed in ClinVar as (likely) pathogenic.

Variant DBs

dbSNP ID	rs368260280
gnomAD	homozygous (T/T)	heterozygous	allele carriers
	0	74	74

Protein conservation

Species	Match	AA	Alignment
Human		667	L	S	N	L	V	A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F	L
mutated	all conserved	667						A	S	L	L	N	S	L	K	S	I	A	S	L	L	L	L	L	F
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

N/A

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	2.735	1
	6.318	1
(flanking)	8.017	1

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

Strand

Original gDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered gDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Original cDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered cDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Wildtype AA sequence

MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
ITMEGWTDVL YWVNDAIGWE WPWVYFVSLI ILGSFFVLNL VLGVLSGEFS KEREKAKARG
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
GEGENRGCCG SLWCWWRRRG AAKAGPSGCR RWGQAISKSK LSRRWRRWNR FNRRRCRAAV
KSVTFYWLVI VLVFLNTLTI SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ
AYFVSLFNRF DCFVVCGGIT ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV
ASLLNSMKSI ASLLLLLFLF IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ
ILTGEDWNAV MYDGIMAYGG PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES
LNTAQKEEAE EKERKKIARK ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP
CDVPVGEEEE EEEEDEPEVP AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH
KLINHHIFTN LILVFIMLSS AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT
FGAFLHKGAF CRNYFNLLDM LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG
LKHVVQCVFV AIRTIGNIMI VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI
LYKDGDVDSP VVRERIWQNS DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP
IYNHRVEISI FFIIYIIIVA FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL
KARPLRRYIP KNPYQYKFWY VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL
NMVFTGVFTV EMVLKVIAFK PKHYFTDAWN TFDALIVVGS VVDIAITEVN PTESENVPVP
TATPGNSEES NRISITFFRL FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL PYVALLIAML
FFIYAVIGMQ MFGKVAMRDN NQINRNNNFQ TFPQAVLLLF RCATGEAWQE IMLACLPGKL
CDPESDYNPG EEYTCGSNFA IVYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH
HLDEFKRIWS EYDPEAKGRI KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVAMNMPLNS
DGTVMFNATL FALVRTALKI KTEGNLEQAN EELRAVIKKI WKKTSMKLLD QVVPPAGGQC
SLFPK*

Mutated AA sequence

MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
ITMEGWTDVL YWVNDAIGWE WPWVYFVSLI ILGSFFVLNL VLGVLSGEFS KEREKAKARG
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
GEGENRGCCG SLWCWWRRRG AAKAGPSGCR RWGQAISKSK LSRRWRRWNR FNRRRCRAAV
KSVTFYWLVI VLVFLNTLTI SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ
AYFVSLFNRF DCFVVCGGIT ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV
ASLLNSLKSI ASLLLLLFLF IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ
ILTGEDWNAV MYDGIMAYGG PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES
LNTAQKEEAE EKERKKIARK ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP
CDVPVGEEEE EEEEDEPEVP AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH
KLINHHIFTN LILVFIMLSS AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT
FGAFLHKGAF CRNYFNLLDM LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG
LKHVVQCVFV AIRTIGNIMI VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI
LYKDGDVDSP VVRERIWQNS DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP
IYNHRVEISI FFIIYIIIVA FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL
KARPLRRYIP KNPYQYKFWY VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL
NMVFTGVFTV EMVLKVIAFK PKHYFTDAWN TFDALIVVGS VVDIAITEVN PTESENVPVP
TATPGNSEES NRISITFFRL FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL PYVALLIAML
FFIYAVIGMQ MFGKVAMRDN NQINRNNNFQ TFPQAVLLLF RCATGEAWQE IMLACLPGKL
CDPESDYNPG EEYTCGSNFA IVYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH
HLDEFKRIWS EYDPEAKGRI KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVAMNMPLNS
DGTVMFNATL FALVRTALKI KTEGNLEQAN EELRAVIKKI WKKTSMKLLD QVVPPAGGQC
SLFPK*

Position of stopcodon in wt / mu CDS

4878 / 4878

Position (AA) of stopcodon in wt / mu AA sequence

1626 / 1626

Position of stopcodon in wt / mu cDNA

5434 / 5434

Position of start ATG in wt / mu cDNA

557 / 557

Last intron/exon boundary

5306

Theoretical NMD boundary in CDS

4699

Length of CDS

4878

Coding sequence (CDS) position

1999

cDNA position

2555

gDNA position

394876

Chromosomal position

53723838

Speed

0.04 s

Back to summary table

Variant:

3:53723838A>T_6_ENST00000636938

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed

Model: simple_aae
Tree vote: 91|9 (del | benign) ?

Analysed issue

Analysis result

Variant

Chr3:53723838A>T (GRCh38)

Gene symbol

CACNA1D

Gene constraints

LOEUF: 0.28, LOF (oe): 0.21, misssense (oe): 0.59, synonymous (oe): 0.93 ? (gnomAD)

Ensembl transcript ID

ENST00000636938.1

Genbank transcript ID

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.1939A>T
g.394876A>T

AA changes

AAE:	M647L	?
Score:	15

Frameshift

Length of protein

Normal

Pathogenic variant (ClinVar)

Variant not listed in ClinVar as (likely) pathogenic.

Variant DBs

dbSNP ID	rs368260280
gnomAD	homozygous (T/T)	heterozygous	allele carriers
	0	74	74

Protein conservation

Species	Match	AA	Alignment
Human		647	L	S	N	L	V	A	S	L	L	N	S	M	K	S	I	A	S	L	L	L	L	L	F	L
mutated	all conserved	647	L	S	N	L	V	A	S	L	L	N	S	L	K	S	I	A	S	L	L	L	L	L	F
Ptroglodytes	no homologue
Mmulatta	no homologue
Fcatus	no homologue
Mmusculus	no homologue
Ggallus	no homologue
Trubripes	no homologue
Drerio	no homologue
Dmelanogaster	no homologue
Celegans	no homologue
Xtropicalis	no homologue

Protein features

N/A

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	2.735	1
	6.318	1
(flanking)	8.017	1

Splice sites

No abrogation of potential splice sites predicted by MaxEntScan.

Distance from splice site

N/A

Kozak consensus sequence altered?

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

Strand

Original gDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered gDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Original cDNA sequence snippet

TGGCATCCTTATTAAACTCCATGAAGTCCATCGCTTCGCTG

Altered cDNA sequence snippet

TGGCATCCTTATTAAACTCCTTGAAGTCCATCGCTTCGCTG

Wildtype AA sequence

MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
ITMEGWTDVL YWVNDAIGWE WPWVYFVSLI ILGSFFVLNL VLGVLSGEFS KEREKAKARG
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
GEGENRGCCG SLCQAISKSK LSRRWRRWNR FNRRRCRAAV KSVTFYWLVI VLVFLNTLTI
SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ AYFVSLFNRF DCFVVCGGIT
ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV ASLLNSMKSI ASLLLLLFLF
IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ ILTGEDWNAV MYDGIMAYGG
PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES LNTAQKEEAE EKERKKIARK
ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP CDVPVGEEEE EEEEDEPEVP
AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH KLINHHIFTN LILVFIMLSS
AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT FGAFLHKGAF CRNYFNLLDM
LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG LKHVVQCVFV AIRTIGNIMI
VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI LYKDGDVDSP VVRERIWQNS
DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP IYNHRVEISI FFIIYIIIVA
FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL KARPLRRYIP KNPYQYKFWY
VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL NMVFTGVFTV EMVLKVIAFK
PKGYFSDAWN TFDSLIVIGS IIDVALSEAD PTESENVPVP TATPGNSEES NRISITFFRL
FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL PYVALLIAML FFIYAVIGMQ MFGKVAMRDN
NQINRNNNFQ TFPQAVLLLF RCATGEAWQE IMLACLPGKL CDPESDYNPG EEYTCGSNFA
IVYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH HLDEFKRIWS EYDPEAKGRI
KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVAMNMPLNS DGTVMFNATL FALVRTALKI
KTEGNLEQAN EELRAVIKKI WKKTSMKLLD QVVPPAGDDE VTVGKFYATF LIQDYFRKFK
KRKEQGLVGK YPAKNTTIAL QMLERML*

Mutated AA sequence

MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC
ITMEGWTDVL YWVNDAIGWE WPWVYFVSLI ILGSFFVLNL VLGVLSGEFS KEREKAKARG
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS
GEGENRGCCG SLCQAISKSK LSRRWRRWNR FNRRRCRAAV KSVTFYWLVI VLVFLNTLTI
SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ AYFVSLFNRF DCFVVCGGIT
ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV ASLLNSLKSI ASLLLLLFLF
IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ ILTGEDWNAV MYDGIMAYGG
PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES LNTAQKEEAE EKERKKIARK
ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP CDVPVGEEEE EEEEDEPEVP
AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH KLINHHIFTN LILVFIMLSS
AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT FGAFLHKGAF CRNYFNLLDM
LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG LKHVVQCVFV AIRTIGNIMI
VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI LYKDGDVDSP VVRERIWQNS
DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP IYNHRVEISI FFIIYIIIVA
FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL KARPLRRYIP KNPYQYKFWY
VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL NMVFTGVFTV EMVLKVIAFK
PKGYFSDAWN TFDSLIVIGS IIDVALSEAD PTESENVPVP TATPGNSEES NRISITFFRL
FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL PYVALLIAML FFIYAVIGMQ MFGKVAMRDN
NQINRNNNFQ TFPQAVLLLF RCATGEAWQE IMLACLPGKL CDPESDYNPG EEYTCGSNFA
IVYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH HLDEFKRIWS EYDPEAKGRI
KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVAMNMPLNS DGTVMFNATL FALVRTALKI
KTEGNLEQAN EELRAVIKKI WKKTSMKLLD QVVPPAGDDE VTVGKFYATF LIQDYFRKFK
KRKEQGLVGK YPAKNTTIAL QMLERML*

Position of stopcodon in wt / mu CDS

4944 / 4944

Position (AA) of stopcodon in wt / mu AA sequence

1648 / 1648

Position of stopcodon in wt / mu cDNA

5437 / 5437

Position of start ATG in wt / mu cDNA

494 / 494

Last intron/exon boundary

5416

Theoretical NMD boundary in CDS

4872

Length of CDS

4944

Coding sequence (CDS) position

1939

cDNA position

2432

gDNA position

394876

Chromosomal position

53723838

Speed

0.05 s

MutationT@ster 2025

Transcript summary:

MutationT@ster 2025

Variant:

3:53723838A>T_5_ENST00000350061

Prediction:

Summary:

MutationT@ster 2025

Variant:

3:53723838A>T_1_ENST00000637424

Prediction:

Summary:

MutationT@ster 2025

Variant:

3:53723838A>T_7_ENST00000636570

Prediction:

Summary:

MutationT@ster 2025

Variant:

3:53723838A>T_8_ENST00000422281

Prediction:

Summary:

MutationT@ster 2025

Variant:

3:53723838A>T_3_ENST00000481478

Prediction:

Summary:

MutationT@ster 2025

Variant:

3:53723838A>T_4_ENST00000288139

Prediction:

Summary:

MutationT@ster 2025

Variant:

3:53723838A>T_9_ENST00000640483

Prediction:

Summary:

MutationT@ster 2025

Variant:

3:53723838A>T_2_ENST00000636627

Prediction:

Summary:

MutationT@ster 2025

Variant:

3:53723838A>T_6_ENST00000636938

Prediction:

Summary: