1-20650507-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032409.3(PINK1):​c.1562A>G​(p.Asn521Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N521T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

PINK1
NM_032409.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.617
Variant links:
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]
PINK1-AS (HGNC:38872): (PINK1 antisense RNA)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04785511).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PINK1NM_032409.3 linkc.1562A>G p.Asn521Ser missense_variant 8/8 ENST00000321556.5 NP_115785.1 Q9BXM7-1
PINK1-ASNR_046507.1 linkn.1687T>C non_coding_transcript_exon_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PINK1ENST00000321556.5 linkc.1562A>G p.Asn521Ser missense_variant 8/81 NM_032409.3 ENSP00000364204.3 Q9BXM7-1
PINK1ENST00000400490.2 linkn.655A>G non_coding_transcript_exon_variant 4/42
PINK1-ASENST00000451424.1 linkn.1687T>C non_coding_transcript_exon_variant 1/32
PINK1ENST00000492302.1 linkn.3012A>G non_coding_transcript_exon_variant 5/52

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
57
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
17
DANN
Benign
0.96
DEOGEN2
Benign
0.066
T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.69
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.048
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.21
N
REVEL
Benign
0.029
Sift
Benign
0.36
T
Sift4G
Benign
0.58
T
Polyphen
0.0030
B
Vest4
0.084
MutPred
0.29
Gain of ubiquitination at K520 (P = 0.1278);
MVP
0.62
MPC
0.14
ClinPred
0.099
T
GERP RS
1.6
Varity_R
0.033
gMVP
0.053

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1043424; hg19: chr1-20977000; API