rs74315360
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The ENST00000321556.5(PINK1):c.650C>A(p.Ala217Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
PINK1
ENST00000321556.5 missense
ENST00000321556.5 missense
Scores
13
5
1
Clinical Significance
Conservation
PhyloP100: 6.59
Genes affected
PINK1 (HGNC:14581): (PTEN induced kinase 1) This gene encodes a serine/threonine protein kinase that localizes to mitochondria. It is thought to protect cells from stress-induced mitochondrial dysfunction. Mutations in this gene cause one form of autosomal recessive early-onset Parkinson disease. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.986
PP5
Variant 1-20638104-C-A is Pathogenic according to our data. Variant chr1-20638104-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 2414.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PINK1 | NM_032409.3 | c.650C>A | p.Ala217Asp | missense_variant | 2/8 | ENST00000321556.5 | NP_115785.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PINK1 | ENST00000321556.5 | c.650C>A | p.Ala217Asp | missense_variant | 2/8 | 1 | NM_032409.3 | ENSP00000364204 | P1 | |
PINK1 | ENST00000492302.1 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive early-onset Parkinson disease 6 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2006 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
A
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of solvent accessibility (P = 0.0354);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at