rs74315355

chr1-20644639-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_032409.3(PINK1):c.926G>A(p.Gly309Asp) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 33)
• Consequence: PINK1 NM_032409.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.63

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)

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934
• PP5: Variant 1-20644639-G-A is Pathogenic according to our data. Variant chr1-20644639-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2404.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PINK1	NM_032409.3	c.926G>A	p.Gly309Asp	missense_variant	4/8	ENST00000321556.5
PINK1-AS	NR_046507.1	n.3981+946C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PINK1	ENST00000321556.5	c.926G>A	p.Gly309Asp	missense_variant	4/8	1	NM_032409.3	P1
PINK1-AS	ENST00000451424.1	n.3981+946C>T		intron_variant, non_coding_transcript_variant		2
PINK1	ENST00000492302.1	n.2014G>A		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal recessive early-onset Parkinson disease 6 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 15, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
Cadd	Pathogenic	30
Dann	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.068	D
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	A
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Pathogenic	0.66
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.78		Loss of catalytic residue at P305 (P = 0.0914);
MVP		0.97
MPC		0.81
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.90
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs74315355; hg19: chr1-20971132;