rs6904579

Positions:

• chr6-162148169-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.534+52962T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,002 control chromosomes in the GnomAD database, including 16,121 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 0.42 (16121 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKN	NM_004562.3	c.534+52962T>C		intron_variant		ENST00000366898.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKN	ENST00000366898.6	c.534+52962T>C		intron_variant		1	NM_004562.3	P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64495 AN: 151882 Hom.: 16108 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.424 AC: 64506 AN: 152002 Hom.: 16121 Cov.: 32 AF XY: 0.423 AC XY: 31436 AN XY: 74276

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.426

Alfa AF: 0.505 Hom.: 5085

Bravo AF: 0.414

Asia WGS AF: 0.305 AC: 1062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.54

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: rs6904579; hg19: chr6-162569201;