mutation t@sting

Prediction

disease causing

Model: simple_aae, prob: 0.99992009838204 (classification due to ClinVar, real probability is shown anyway) (explain)

Summary

amino acid sequence changed
heterozygous in TGP or ExAC
known disease mutation at this position (HGMD CM920019)
known disease mutation: rs13670 (pathogenic)
protein features (might be) affected
splice site changes

hyperlink

analysed issue

analysis result

name of alteration

no title

alteration (phys. location)

chr1:21890632G>AN/A show variant in all transcripts IGV

HGNC symbol

ALPL

Ensembl transcript ID

ENST00000540617

Genbank transcript ID

NM_001127501

UniProt peptide

P05186

alteration type

single base exchange

alteration region

CDS

DNA changes

c.406G>A
cDNA.663G>A
g.54775G>A

AA changes

E136K Score: 56 explain score(s)

position(s) of altered AA
if AA alteration in CDS

136

frameshift

known variant

Reference ID: rs121918007

database	homozygous (A/A)	heterozygous	allele carriers
1000G	0	4	4
ExAC	1	310	311

known disease mutation: rs13670 (pathogenic for Infantile hypophosphatasia|Adult hypophosphatasia|Childhood hypophosphatasia|Odontohypophosphatasia|Hypophosphatasia|not provided) dbSNP NCBI variation viewer
known disease mutation at this position, please check HGMD for details (HGMD ID CM920019)

known disease mutation at this position, please check HGMD for details (HGMD ID CM920019)
known disease mutation at this position, please check HGMD for details (HGMD ID CM920019)

regulatory features

H3K27me3, Histone, Histone 3 Lysine 27 Tri-Methylation
H3K36me3, Histone, Histone 3 Lysine 36 Tri-Methylation

phyloP / phastCons

	PhyloP	PhastCons
(flanking)	-0.298	0.721
	5.174	1
(flanking)	2.735	1

explain score(s) and/or inspect your position(s) in in UCSC Genome Browser

splice sites

effect	gDNA position	score	wt detection sequence	exon-intron border
Donor marginally increased	54772	wt: 0.2065 / mu: 0.2167 (marginal change - not scored)	wt: CAGACAACGAGATGC mu: CAGACAACAAGATGC	GACA\|acga
Donor increased	54776	wt: 0.52 / mu: 0.74	wt: CAACGAGATGCCCCC mu: CAACAAGATGCCCCC	ACGA\|gatg
Donor increased	54771	wt: 0.26 / mu: 0.94	wt: TCAGACAACGAGATG mu: TCAGACAACAAGATG	AGAC\|aacg

distance from splice site

Kozak consensus sequence altered?

N/A

conservation
protein level for non-synonymous changes

species

match

gene

alignment

Human

136

mutated

all conserved

136

Ptroglodytes

no homologue

Mmulatta

all identical

ENSMMUG00000002217

191

Fcatus

all identical

ENSFCAG00000002960

191

Mmusculus

all identical

ENSMUSG00000028766

191

Ggallus

no homologue

Trubripes

not conserved

ENSTRUG00000004463

192

Drerio

all conserved

ENSDARG00000015546

228

Dmelanogaster

all identical

FBgn0043791

228

Celegans

no homologue

Xtropicalis

no homologue

protein features

start (aa)	end (aa)	feature	details
140	140	CARBOHYD	N-linked (GlcNAc...) (Potential).	might get lost (downstream of altered splice site)
173	173	METAL	Magnesium (Potential).	might get lost (downstream of altered splice site)
230	230	CARBOHYD	N-linked (GlcNAc...) (Potential).	might get lost (downstream of altered splice site)
271	271	CARBOHYD	N-linked (GlcNAc...) (Potential).	might get lost (downstream of altered splice site)
303	303	CARBOHYD	N-linked (GlcNAc...) (Potential).	might get lost (downstream of altered splice site)
332	332	METAL	Magnesium (Potential).	might get lost (downstream of altered splice site)
337	337	METAL	Zinc 1 (Potential).	might get lost (downstream of altered splice site)
341	341	METAL	Zinc 1 (Potential).	might get lost (downstream of altered splice site)
361	361	CONFLICT	Q -> H (in Ref. 1; BAA32129).	might get lost (downstream of altered splice site)
378	378	METAL	Zinc 2 (Potential).	might get lost (downstream of altered splice site)
379	379	METAL	Zinc 2 (Potential).	might get lost (downstream of altered splice site)
430	430	CARBOHYD	N-linked (GlcNAc...).	might get lost (downstream of altered splice site)
446	446	CONFLICT	A -> P (in Ref. 1; BAA32129).	might get lost (downstream of altered splice site)
454	454	METAL	Zinc 1 (Potential).	might get lost (downstream of altered splice site)
502	502	LIPID	GPI-anchor amidated serine (Probable).	might get lost (downstream of altered splice site)
503	524	PROPEP	Removed in mature form (Probable). /FTId=PRO_0000024024.	might get lost (downstream of altered splice site)

length of protein

normal

AA sequence altered

yes

position of stopcodon in wt / mu CDS

1410 / 1410

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

470 / 470

position of stopcodon in wt / mu cDNA

1667 / 1667

poly(A) signal

N/A

conservation
nucleotide level for all changes - no scoring up to now

N/A

position of start ATG in wt / mu cDNA

258 / 258

chromosome

strand

last intron/exon boundary

1402

theoretical NMD boundary in CDS

1094

length of CDS

1410

coding sequence (CDS) position

406

cDNA position
(for ins/del: last normal base / first normal base)

663

gDNA position
(for ins/del: last normal base / first normal base)

54775

chromosomal position
(for ins/del: last normal base / first normal base)

21890632

original gDNA sequence snippet

GGGACTGGTACTCAGACAACGAGATGCCCCCTGAGGCCTTG

altered gDNA sequence snippet

GGGACTGGTACTCAGACAACAAGATGCCCCCTGAGGCCTTG

original cDNA sequence snippet

GGGACTGGTACTCAGACAACGAGATGCCCCCTGAGGCCTTG

altered cDNA sequence snippet

GGGACTGGTACTCAGACAACAAGATGCCCCCTGAGGCCTTG

wildtype AA sequence

MFLGDGMGVS TVTAARILKG QLHHNPGEET RLEMDKFPFV ALSKTYNTNA QVPDSAGTAT
AYLCGVKANE GTVGVSAATE RSRCNTTQGN EVTSILRWAK DAGKSVGIVT TTRVNHATPS
AAYAHSADRD WYSDNEMPPE ALSQGCKDIA YQLMHNIRDI DVIMGGGRKY MYPKNKTDVE
YESDEKARGT RLDGLDLVDT WKSFKPRYKH SHFIWNRTEL LTLDPHNVDY LLGLFEPGDM
QYELNRNNVT DPSLSEMVVV AIQILRKNPK GFFLLVEGGR IDHGHHEGKA KQALHEAVEM
DRAIGQAGSL TSSEDTLTVV TADHSHVFTF GGYTPRGNSI FGLAPMLSDT DKKPFTAILY
GNGPGYKVVG GERENVSMVD YAHNNYQAQS AVPLRHETHG GEDVAVFSKG PMAHLLHGVH
EQNYVPHVMA YAACIGANLG HCAPASSAGS LAAGPLLLAL ALYPLSVLF*

mutated AA sequence

MFLGDGMGVS TVTAARILKG QLHHNPGEET RLEMDKFPFV ALSKTYNTNA QVPDSAGTAT
AYLCGVKANE GTVGVSAATE RSRCNTTQGN EVTSILRWAK DAGKSVGIVT TTRVNHATPS
AAYAHSADRD WYSDNKMPPE ALSQGCKDIA YQLMHNIRDI DVIMGGGRKY MYPKNKTDVE
YESDEKARGT RLDGLDLVDT WKSFKPRYKH SHFIWNRTEL LTLDPHNVDY LLGLFEPGDM
QYELNRNNVT DPSLSEMVVV AIQILRKNPK GFFLLVEGGR IDHGHHEGKA KQALHEAVEM
DRAIGQAGSL TSSEDTLTVV TADHSHVFTF GGYTPRGNSI FGLAPMLSDT DKKPFTAILY
GNGPGYKVVG GERENVSMVD YAHNNYQAQS AVPLRHETHG GEDVAVFSKG PMAHLLHGVH
EQNYVPHVMA YAACIGANLG HCAPASSAGS LAAGPLLLAL ALYPLSVLF*

speed

1.07 s

All positions are in basepairs (bp) if not explicitly stated differently.
AA/aa: amino acid; CDS: coding sequence; mu: mutated; NMD: nonsense-mediated mRNA decay; nt: nucleotide; wt: wildtype; TGP: 1000 Genomes Project