rs9456676

Variant names:

• chr6-161478212-C-T
• rs9456676
• NM_004562.3:c.1083+70642G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004562.3(PRKN):​c.1083+70642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,048 control chromosomes in the GnomAD database, including 3,676 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3676 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.61
• Publications: 5 publications found

Genes affected

PRKN (HGNC:8607): (parkin RBR E3 ubiquitin protein ligase) The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq, Jul 2008]

PRKN Gene-Disease associations (from GenCC):

• autosomal recessive juvenile Parkinson disease 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp
• Parkinson disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• young-onset Parkinson disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC105378098 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.1083+70642G>A		intron_variant	Intron 9 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.1083+70642G>A		intron_variant	Intron 9 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30973 AN: 151932 Hom.: 3666 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.0980

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.192

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.204 AC: 31028 AN: 152048 Hom.: 3676 Cov.: 32 AF XY: 0.201 AC XY: 14961 AN XY: 74310

African (AFR) AF: 0.328 AC: 13618 AN: 41464

American (AMR) AF: 0.159 AC: 2437 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 615 AN: 3470

East Asian (EAS) AF: 0.140 AC: 720 AN: 5156

South Asian (SAS) AF: 0.174 AC: 838 AN: 4818

European-Finnish (FIN) AF: 0.177 AC: 1867 AN: 10568

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10367 AN: 67974

Other (OTH) AF: 0.196 AC: 414 AN: 2114

Alfa AF: 0.167 Hom.: 4290

Bravo AF: 0.209

Asia WGS AF: 0.172 AC: 597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.037
DANN	Benign	0.56
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs9456676; hg19: chr6-161899244;