6-162558115-C-T

Position:

• chr6-162558115-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004562.3(PRKN):​c.8-114642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,860 control chromosomes in the GnomAD database, including 22,546 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 0.54 (22546 hom., cov: 31)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.675

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKN	NM_004562.3	c.8-114642G>A		intron_variant		ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.8-114642G>A		intron_variant		1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82028 AN: 151744 Hom.: 22517 Cov.: 31

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.541 AC: 82097 AN: 151860 Hom.: 22546 Cov.: 31 AF XY: 0.546 AC XY: 40485 AN XY: 74180

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.536

Alfa AF: 0.446 Hom.: 2019

Bravo AF: 0.545

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.79

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: rs4636000; hg19: chr6-162979147; COSMIC: COSV58211436;