rs6904579

Variant names:

• chr6-162148169-A-G
• rs6904579
• NM_004562.3:c.534+52962T>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.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
• Publications: 7 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=-0.86).
• 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 rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.534+52962T>C		intron_variant	Intron 4 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.534+52962T>C		intron_variant	Intron 4 of 11	1	NM_004562.3	ENSP00000355865.1

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

African (AFR) AF: 0.153 AC: 6358 AN: 41466

American (AMR) AF: 0.503 AC: 7677 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1710 AN: 3466

East Asian (EAS) AF: 0.276 AC: 1425 AN: 5168

South Asian (SAS) AF: 0.416 AC: 2004 AN: 4820

European-Finnish (FIN) AF: 0.556 AC: 5866 AN: 10554

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38049 AN: 67960

Other (OTH) AF: 0.426 AC: 899 AN: 2108

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
PhyloP100		1.1
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: rs6904579; hg19: chr6-162569201;