rs6931162

chr6-162522510-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PRKN	NM_004562.3	c.8-79037T>C		intron_variant		ENST00000366898.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKN	ENST00000366898.6	c.8-79037T>C		intron_variant		1	NM_004562.3	P1

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

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.0811

Gnomad4 ASJ AF: 0.0953

Gnomad4 EAS AF: 0.0359

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.0615

Gnomad4 NFE AF: 0.0816

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.0884 Hom.: 215

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6931162; hg19: chr6-162943542;