rs6931162

Variant names:

• chr6-162522510-A-G
• rs6931162
• NM_004562.3:c.8-79037T>C

Variant summary

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

The NM_004562.3(PRKN):​c.8-79037T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 152,318 control chromosomes in the GnomAD database, including 673 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 0.090 (673 hom., cov: 33)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 4 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.8-79037T>C		intron_variant	Intron 1 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.8-79037T>C		intron_variant	Intron 1 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.0902 AC: 13723 AN: 152200 Hom.: 674 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.0366

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0615

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0816

Gnomad OTH AF: 0.0836

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

GnomAD4 genome AF: 0.0901 AC: 13724 AN: 152318 Hom.: 673 Cov.: 33 AF XY: 0.0902 AC XY: 6716 AN XY: 74468

African (AFR) AF: 0.110 AC: 4570 AN: 41568

American (AMR) AF: 0.0811 AC: 1240 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0953 AC: 331 AN: 3472

East Asian (EAS) AF: 0.0359 AC: 186 AN: 5182

South Asian (SAS) AF: 0.179 AC: 862 AN: 4824

European-Finnish (FIN) AF: 0.0615 AC: 653 AN: 10618

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0816 AC: 5551 AN: 68036

Other (OTH) AF: 0.0851 AC: 180 AN: 2116

Alfa AF: 0.0897 Hom.: 273

Bravo AF: 0.0894

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.3
DANN	Benign	0.41
PhyloP100		-0.42
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: rs6931162; hg19: chr6-162943542;