rs3131713

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032409.3(PINK1):c.960-5G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 1,611,824 control chromosomes in the GnomAD database, including 610,277 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 53621 hom., cov: 27)

Exomes 𝑓: 0.87 ( 556656 hom. )

Consequence

PINK1
NM_032409.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002494

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -2.90

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-AS (HGNC:38872): (PINK1 antisense RNA)

PINK1-AS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 1-20645555-G-A is Benign according to our data. Variant chr1-20645555-G-A is described in ClinVar as [Benign]. Clinvar id is 262028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-20645555-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PINK1	NM_032409.3 linkuse as main transcript	c.960-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000321556.5
PINK1-AS	NR_046507.1 linkuse as main transcript	n.3981+30C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PINK1	ENST00000321556.5 linkuse as main transcript	c.960-5G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_032409.3	P1	Q9BXM7-1
PINK1-AS	ENST00000451424.1 linkuse as main transcript	n.3981+30C>T	intron_variant, non_coding_transcript_variant		2
PINK1	ENST00000400490.2 linkuse as main transcript	n.48G>A	non_coding_transcript_exon_variant	1/4	2
PINK1	ENST00000492302.1 linkuse as main transcript	n.2048-5G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.842

AC:

126742

AN:

150610

Hom.:

53586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.765

Gnomad AMI

AF:

0.838

Gnomad AMR

AF:

0.811

Gnomad ASJ

AF:

0.903

Gnomad EAS

AF:

0.794

Gnomad SAS

AF:

0.883

Gnomad FIN

AF:

0.927

Gnomad MID

AF:

0.899

Gnomad NFE

AF:

0.878

Gnomad OTH

AF:

0.863

GnomAD3 exomes

AF:

0.862

AC:

216185

AN:

250826

Hom.:

93518

AF XY:

0.867

AC XY:

117629

AN XY:

135624

show subpopulations

Gnomad AFR exome

AF:

0.767

Gnomad AMR exome

AF:

0.809

Gnomad ASJ exome

AF:

0.900

Gnomad EAS exome

AF:

0.808

Gnomad SAS exome

AF:

0.886

Gnomad FIN exome

AF:

0.930

Gnomad NFE exome

AF:

0.877

Gnomad OTH exome

AF:

0.872

GnomAD4 exome

AF:

0.872

AC:

1274286

AN:

1461098

Hom.:

556656

Cov.:

AF XY:

0.873

AC XY:

634719

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.755

Gnomad4 AMR exome

AF:

0.807

Gnomad4 ASJ exome

AF:

0.900

Gnomad4 EAS exome

AF:

0.789

Gnomad4 SAS exome

AF:

0.884

Gnomad4 FIN exome

AF:

0.927

Gnomad4 NFE exome

AF:

0.877

Gnomad4 OTH exome

AF:

0.869

GnomAD4 genome

AF:

0.841

AC:

126826

AN:

150726

Hom.:

53621

Cov.:

AF XY:

0.844

AC XY:

61980

AN XY:

73458

show subpopulations

Gnomad4 AFR

AF:

0.765

Gnomad4 AMR

AF:

0.810

Gnomad4 ASJ

AF:

0.903

Gnomad4 EAS

AF:

0.794

Gnomad4 SAS

AF:

0.884

Gnomad4 FIN

AF:

0.927

Gnomad4 NFE

AF:

0.878

Gnomad4 OTH

AF:

0.864

Alfa

AF:

0.872

Hom.:

28261

Bravo

AF:

0.830

Asia WGS

AF:

0.818

AC:

2843

AN:

3476

EpiCase

AF:

0.880

EpiControl

AF:

0.883

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 31, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 90% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 84. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 08, 2019	- -

Autosomal recessive early-onset Parkinson disease 6

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.29

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00025

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.080

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.

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