Variant 1-20650512-A-AAGTT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5

The NM_032409.3(PINK1):c.1570_1573dupTTAG(p.Asp525fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

PINK1
NM_032409.3 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.15

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 links:

PINK1 (HGNC:):

PINK1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0985 CDS is truncated, and there are 3 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-20650512-A-AAGTT is Pathogenic according to our data. Variant chr1-20650512-A-AAGTT is described in ClinVar as [Pathogenic]. Clinvar id is 2409.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 linkuse as main transcript	c.1570_1573dupTTAG	p.Asp525fs	frameshift_variant	8/8	ENST00000321556.5	NP_115785.1	Q9BXM7-1
PINK1-AS	NR_046507.1 linkuse as main transcript	n.1678_1681dupAACT		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PINK1	ENST00000321556.5 linkuse as main transcript	c.1570_1573dupTTAG	p.Asp525fs	frameshift_variant	8/8	1	NM_032409.3	ENSP00000364204.3	Q9BXM7-1
PINK1	ENST00000400490.2 linkuse as main transcript	n.663_666dupTTAG		non_coding_transcript_exon_variant	4/4	2
PINK1-AS	ENST00000451424.1 linkuse as main transcript	n.1678_1681dupAACT		non_coding_transcript_exon_variant	1/3	2
PINK1	ENST00000492302.1 linkuse as main transcript	n.3020_3023dupTTAG		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over