MutationT@ster 2025

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Input seems to be ok - now mapping the variant to the different transcripts...
Querying Taster for transcript #1: ENST00000553106
Querying Taster for transcript #2: ENST00000307000
MT speed 0.09 s - this script 2.518115 s

Transcript summary:

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Transcript	Gene symbol	Prediction	Tree vote	Model	Prediction problem	Splice site change	Known ClinVar disease mutation	Potential ClinVar disease mutation	Amino acid changes	Variant type	dbSNP ID	Protein length	Features at a glance
ENST00000307000	PAH	Deleterious	97\|3	simple_aae		Yes	Yes			Single base exchange		Normal	Amino acid sequence changed Known disease mutation: ClinVar ID 1334639 (pathogenic) Splice site changes
ENST00000553106(MANE Select)	PAH	Deleterious	98\|2	simple_aae		Yes	Yes			Single base exchange		Normal	Amino acid sequence changed Known disease mutation: ClinVar ID 1334639 (pathogenic) Protein features (might be) affected Splice site changes

MutationT@ster 2025

Variant:

12:102852815G>T_2_ENST00000307000

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Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 1334639 (pathogenic)
Splice site changes

Model: simple_aae
Tree vote: 97|3 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr12:102852815G>T (GRCh38)

Gene symbol

PAH

Gene constraints

LOEUF: 1.28, LOF (oe): 1.02, misssense (oe): 1.00, synonymous (oe): 0.94 ? (gnomAD)

Ensembl transcript ID

ENST00000307000.7

Genbank transcript ID

UniProt / AlphaMissense peptide

N/A

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.827C>A
g.105596C>A

AA changes

AAE:	P276H	?
Score:	77

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Phenylketonuria

pathogenic

ClinVar OMIM

Variant DBs

dbSNP ID	rs5030851
gnomAD	homozygous (T/T)	heterozygous	allele carriers
	0	3	3

Protein conservation

Species	Match	AA	Alignment
Human		276	R	H	G	S	K	P	M	Y	T	P	E	P	D	I	C	H	E	L	L	G	H	V	P	L
mutated	not conserved	276	R	H	G	S	K	P	M	Y	T	P	E	H	D	I	C	H	E	L	L	G	H	V	P
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)	7.905	1
	10.003	1
(flanking)	10.003	1

?

Splice sites

MaxEntScan:

effect	gDNA position	score	sequence	exon-intron border
Donor weakened	105596	wt: 9.40 / mu: 8.34	-	wt: CCCCCGAACC\|gtgagtactg mu: CCCCCGAACA\|gtgagtactg

Distance from splice site

1

Kozak consensus sequence altered?

No

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

12

Strand

-1

Original gDNA sequence snippet

GCCCATGTATACCCCCGAACCGTGAGTACTGTCCTCCAGCT

Altered gDNA sequence snippet

GCCCATGTATACCCCCGAACAGTGAGTACTGTCCTCCAGCT

Original cDNA sequence snippet

GCCCATGTATACCCCCGAACCTGACATCTGCCATGAGCTGT

Altered cDNA sequence snippet

GCCCATGTATACCCCCGAACATGACATCTGCCATGAGCTGT

Wildtype AA sequence

MSALTPTLVF CHMHVETSYI EDNCNQNGAI SLIFSLKEEV GALAKVLRLF EENDVNLTHI
ESRPSRLKKD EYEFFTHLDK RSLPALTNII KILRHDIGAT VHELSRDKKK DTVPWFPRTI
QELDRFANQI LSYGAELDAD HPGFKDPVYR ARRKQFADIA YNYRHGQPIP RVEYMEEEKK
TWGTVFKTLK SLYKTHACYE YNHIFPLLEK YCGFHEDNIP QLEDVSQFLQ TCTGFRLRPV
AGLLSSRDFL GGLAFRVFHC TQYIRHGSKP MYTPEPDICH ELLGHVPLFS DRSFAQFSQE
IGLASLGAPD EYIEKLATIY WFTVEFGLCK QGDSIKAYGA GLLSSFGELQ YCLSEKPKLL
PLELEKTAIQ NYTVTEFQPL YYVAESFNDA KEKVRNFAAT IPRPFSVRYD PYTQRIEVLD
NTQQLKILAD SINSEIGILC SALQKIK*

Mutated AA sequence

MSALTPTLVF CHMHVETSYI EDNCNQNGAI SLIFSLKEEV GALAKVLRLF EENDVNLTHI
ESRPSRLKKD EYEFFTHLDK RSLPALTNII KILRHDIGAT VHELSRDKKK DTVPWFPRTI
QELDRFANQI LSYGAELDAD HPGFKDPVYR ARRKQFADIA YNYRHGQPIP RVEYMEEEKK
TWGTVFKTLK SLYKTHACYE YNHIFPLLEK YCGFHEDNIP QLEDVSQFLQ TCTGFRLRPV
AGLLSSRDFL GGLAFRVFHC TQYIRHGSKP MYTPEHDICH ELLGHVPLFS DRSFAQFSQE
IGLASLGAPD EYIEKLATIY WFTVEFGLCK QGDSIKAYGA GLLSSFGELQ YCLSEKPKLL
PLELEKTAIQ NYTVTEFQPL YYVAESFNDA KEKVRNFAAT IPRPFSVRYD PYTQRIEVLD
NTQQLKILAD SINSEIGILC SALQKIK*

Position of stopcodon in wt / mu CDS

1344 / 1344

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

448 / 448

Position of stopcodon in wt / mu cDNA

1615 / 1615

Position of start ATG in wt / mu cDNA

272 / 272

Last intron/exon boundary

1571

Theoretical NMD boundary in CDS

1249

Length of CDS

1344

Coding sequence (CDS) position

827

cDNA position

1098

gDNA position

105596

Chromosomal position

102852815

Speed

0.04 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

MutationT@ster 2025

Variant:

12:102852815G>T_1_ENST00000553106

Back to summary table

Prediction:

DeleteriousPermalink

Summary:

Amino acid sequence changed
Known disease mutation: ClinVar ID 1334639 (pathogenic)
Protein features (might be) affected
Splice site changes

Model: simple_aae
Tree vote: 98|2 (del | benign) ?
Automatic classification due to ClinVar

Analysed issue

Analysis result

Variant

Chr12:102852815G>T (GRCh38)

Gene symbol

PAH

Gene constraints

LOEUF: 1.26, LOF (oe): 1.01, misssense (oe): 1.00, synonymous (oe): 0.94 ? (gnomAD)

Ensembl transcript ID

ENST00000553106.6

Genbank transcript ID

NM_000277 (exact from MANE), NM_001354304 (by similarity)

UniProt / AlphaMissense peptide

PH4H_HUMAN | AlphaMissense: transcript, gene

Variant type

Single base exchange

Gene region

CDS

DNA changes

c.842C>A
g.105596C>A

AA changes

AAE:	P281H	?
Score:	77

Frameshift

No

Length of protein

Normal

Pathogenic variant (ClinVar)

Phenylketonuria

pathogenic

ClinVar OMIM

Variant DBs

dbSNP ID	rs5030851
gnomAD	homozygous (T/T)	heterozygous	allele carriers
	0	3	3

Protein conservation

Species	Match	AA	Alignment
Human		281	R	H	G	S	K	P	M	Y	T	P	E	P	D	I	C	H	E	L	L	G	H	V	P	L
mutated	not conserved	281	R	H	G	S	K	P	M	Y	T	P	E	H	D	I	C	H	E	L	L	G	H	V	P
Ptroglodytes	all identical	281	R	H	G	S	K	P	M	Y	T	P	E	P	D	I	C	H	E	L	L	G	H	V	P
Mmulatta	all identical	281	R	H	G	S	K	P	M	Y	T	P	E	P	D	I	C	H	E	L	L	G	H	V	P
Fcatus	all identical	280	R	H	G	S	K	P	M	Y	T	P	E	P	D	I	C	H	E	L	L	G	H	V	P
Mmusculus	all identical	281	R	H	G	S	K	P	M	Y	T	P	E	P	D	I	C	H	E	L	L	G	H	V	P
Ggallus	all identical	275	R	H	A	S	K	P	M	Y	T	P	E	P	D	I	C	H	E	L	L	G	H	V	P
Trubripes	all identical	291	R	H	S	S	R	P	T	Y	T	P	E	P	D	V	C	H	E	L	L	G	H	V	P
Drerio	no homologue
Dmelanogaster	all identical	280	R	H	P	S	K	P	M	Y	T	P	E	P	D	V	C	H	E	L	M	G	H	V	P
Celegans	all identical	281	R	H	H	S	A	P	K	Y	T	P	E	P	D	I	C	H	E	L	L	G	H	V	P
Xtropicalis	no homologue

Protein features

Start (aa)	End (aa)	Feature	Details
1	452	CHAIN		lost

Phylogenetic conservation

	PhyloP	PhastCons
(flanking)	7.905	1
	10.003	1
(flanking)	10.003	1

?

Splice sites

MaxEntScan:

effect	gDNA position	score	sequence	exon-intron border
Donor weakened	105596	wt: 9.40 / mu: 8.34	-	wt: CCCCCGAACC\|gtgagtactg mu: CCCCCGAACA\|gtgagtactg

Distance from splice site

1

Kozak consensus sequence altered?

No

poly(A) signal

N/A

AA sequence altered

Yes

Chromosome

12

Strand

-1

Original gDNA sequence snippet

GCCCATGTATACCCCCGAACCGTGAGTACTGTCCTCCAGCT

Altered gDNA sequence snippet

GCCCATGTATACCCCCGAACAGTGAGTACTGTCCTCCAGCT

Original cDNA sequence snippet

GCCCATGTATACCCCCGAACCTGACATCTGCCATGAGCTGT

Altered cDNA sequence snippet

GCCCATGTATACCCCCGAACATGACATCTGCCATGAGCTGT

Wildtype AA sequence

MSTAVLENPG LGRKLSDFGQ ETSYIEDNCN QNGAISLIFS LKEEVGALAK VLRLFEENDV
NLTHIESRPS RLKKDEYEFF THLDKRSLPA LTNIIKILRH DIGATVHELS RDKKKDTVPW
FPRTIQELDR FANQILSYGA ELDADHPGFK DPVYRARRKQ FADIAYNYRH GQPIPRVEYM
EEEKKTWGTV FKTLKSLYKT HACYEYNHIF PLLEKYCGFH EDNIPQLEDV SQFLQTCTGF
RLRPVAGLLS SRDFLGGLAF RVFHCTQYIR HGSKPMYTPE PDICHELLGH VPLFSDRSFA
QFSQEIGLAS LGAPDEYIEK LATIYWFTVE FGLCKQGDSI KAYGAGLLSS FGELQYCLSE
KPKLLPLELE KTAIQNYTVT EFQPLYYVAE SFNDAKEKVR NFAATIPRPF SVRYDPYTQR
IEVLDNTQQL KILADSINSE IGILCSALQK IK*

Mutated AA sequence

MSTAVLENPG LGRKLSDFGQ ETSYIEDNCN QNGAISLIFS LKEEVGALAK VLRLFEENDV
NLTHIESRPS RLKKDEYEFF THLDKRSLPA LTNIIKILRH DIGATVHELS RDKKKDTVPW
FPRTIQELDR FANQILSYGA ELDADHPGFK DPVYRARRKQ FADIAYNYRH GQPIPRVEYM
EEEKKTWGTV FKTLKSLYKT HACYEYNHIF PLLEKYCGFH EDNIPQLEDV SQFLQTCTGF
RLRPVAGLLS SRDFLGGLAF RVFHCTQYIR HGSKPMYTPE HDICHELLGH VPLFSDRSFA
QFSQEIGLAS LGAPDEYIEK LATIYWFTVE FGLCKQGDSI KAYGAGLLSS FGELQYCLSE
KPKLLPLELE KTAIQNYTVT EFQPLYYVAE SFNDAKEKVR NFAATIPRPF SVRYDPYTQR
IEVLDNTQQL KILADSINSE IGILCSALQK IK*

Position of stopcodon in wt / mu CDS

1359 / 1359

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

453 / 453

Position of stopcodon in wt / mu cDNA

1473 / 1473

Position of start ATG in wt / mu cDNA

115 / 115

Last intron/exon boundary

1429

Theoretical NMD boundary in CDS

1264

Length of CDS

1359

Coding sequence (CDS) position

842

cDNA position

956

gDNA position

105596

Chromosomal position

102852815

Speed

0.05 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