rs74315356
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_032409.3(PINK1):c.1311G>A(p.Trp437Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
PINK1
NM_032409.3 stop_gained
NM_032409.3 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 8.98
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-20649054-G-A is Pathogenic according to our data. Variant chr1-20649054-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2406.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-20649054-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PINK1 | NM_032409.3 | c.1311G>A | p.Trp437Ter | stop_gained | 7/8 | ENST00000321556.5 | |
PINK1-AS | NR_046507.1 | n.3140C>T | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PINK1 | ENST00000321556.5 | c.1311G>A | p.Trp437Ter | stop_gained | 7/8 | 1 | NM_032409.3 | P1 | |
PINK1-AS | ENST00000451424.1 | n.3140C>T | non_coding_transcript_exon_variant | 1/3 | 2 | ||||
PINK1 | ENST00000400490.2 | n.404G>A | non_coding_transcript_exon_variant | 3/4 | 2 | ||||
PINK1 | ENST00000492302.1 | n.2761G>A | non_coding_transcript_exon_variant | 4/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152278Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
2
AN:
152278
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251218Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135808
GnomAD3 exomes
AF:
AC:
1
AN:
251218
Hom.:
AF XY:
AC XY:
1
AN XY:
135808
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461762Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727180
GnomAD4 exome
AF:
AC:
6
AN:
1461762
Hom.:
Cov.:
31
AF XY:
AC XY:
4
AN XY:
727180
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152278Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74398
GnomAD4 genome
?
AF:
AC:
2
AN:
152278
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74398
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
1
EpiCase
AF:
EpiControl
AF:
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, 2008 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A
Vest4
GERP RS
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