rs3131713

Variant names:

• chr1-20645555-G-A
• rs3131713
• NM_032409.3:c.960-5G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-20645555-G-A
• chr1-20645555-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032409.3(PINK1):​c.960-5G>A variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.0002494
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -2.90
• Publications: 25 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: Benign. The variant received -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 VariationId is 262028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

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.960-5G>A		splice_region intron	N/A	NP_115785.1
	PINK1-AS	NR_046507.1		n.3981+30C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINK1	ENST00000321556.5	TSL:1 MANE Select	c.960-5G>A		splice_region intron	N/A	ENSP00000364204.3
	PINK1	ENST00000400490.2	TSL:2	n.48G>A		non_coding_transcript_exon	Exon 1 of 4
	PINK1-AS	ENST00000451424.1	TSL:2	n.3981+30C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.842 AC: 126742 AN: 150610 Hom.: 53586 Cov.: 27

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

GnomAD2 exomes AF: 0.862 AC: 216185 AN: 250826 AF XY: 0.867

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 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.: 57 AF XY: 0.873 AC XY: 634719 AN XY: 726872

African (AFR) AF: 0.755 AC: 25282 AN: 33464

American (AMR) AF: 0.807 AC: 36080 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 23530 AN: 26134

East Asian (EAS) AF: 0.789 AC: 31320 AN: 39686

South Asian (SAS) AF: 0.884 AC: 76244 AN: 86254

European-Finnish (FIN) AF: 0.927 AC: 49010 AN: 52864

Middle Eastern (MID) AF: 0.909 AC: 5238 AN: 5764

European-Non Finnish (NFE) AF: 0.877 AC: 975100 AN: 1111842

Other (OTH) AF: 0.869 AC: 52482 AN: 60374

GnomAD4 genome AF: 0.841 AC: 126826 AN: 150726 Hom.: 53621 Cov.: 27 AF XY: 0.844 AC XY: 61980 AN XY: 73458

African (AFR) AF: 0.765 AC: 31252 AN: 40846

American (AMR) AF: 0.810 AC: 12227 AN: 15096

Ashkenazi Jewish (ASJ) AF: 0.903 AC: 3130 AN: 3468

East Asian (EAS) AF: 0.794 AC: 4054 AN: 5106

South Asian (SAS) AF: 0.884 AC: 4229 AN: 4786

European-Finnish (FIN) AF: 0.927 AC: 9477 AN: 10218

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.878 AC: 59617 AN: 67902

Other (OTH) AF: 0.864 AC: 1813 AN: 2098

Alfa AF: 0.862 Hom.: 102225

Bravo AF: 0.830

Asia WGS AF: 0.818 AC: 2843 AN: 3476

EpiCase AF: 0.880

EpiControl AF: 0.883

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Autosomal recessive early-onset Parkinson disease 6 (3)
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.29
DANN	Benign	0.86
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3131713; hg19: chr1-20972048;