chr1-20650512-A-AAGTT

Variant names:

• chr1-20650512-A-AAGTT
• rs730880302
• NM_032409.3:c.1570_1573dupTTAG

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_Moderate PM2 PP5

The NM_032409.3(PINK1):​c.1570_1573dupTTAG​(p.Asp525ValfsTer38) 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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.15
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 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 VariationId is 2409.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032409.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINK1	NM_032409.3	MANE Select	c.1570_1573dupTTAG	p.Asp525ValfsTer38	frameshift	Exon 8 of 8	NP_115785.1
	PINK1-AS	NR_046507.1		n.1678_1681dupAACT		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINK1	ENST00000321556.5	TSL:1 MANE Select	c.1570_1573dupTTAG	p.Asp525ValfsTer38	frameshift	Exon 8 of 8	ENSP00000364204.3
	PINK1	ENST00000400490.2	TSL:2	n.663_666dupTTAG		non_coding_transcript_exon	Exon 4 of 4
	PINK1-AS	ENST00000451424.1	TSL:2	n.1678_1681dupAACT		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

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

Sep 01, 2004

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1
Mutation Taster		=16/184	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs730880302; hg19: chr1-20977005;