rs9364628

chr6-161918254-T-Cchr6-161918254-T-G

Variant summary

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

The NM_004562.3(PRKN):c.734+55048A>G variant causes a intron change. The variant allele was found at a frequency of 0.473 in 152,000 control chromosomes in the GnomAD database, including 17,684 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 0.47 (17684 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.77

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=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKN	NM_004562.3	c.734+55048A>G		intron_variant		ENST00000366898.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKN	ENST00000366898.6	c.734+55048A>G		intron_variant		1	NM_004562.3	P1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71808 AN: 151882 Hom.: 17651 Cov.: 32

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.473 AC: 71888 AN: 152000 Hom.: 17684 Cov.: 32 AF XY: 0.471 AC XY: 34958 AN XY: 74282

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.462

Alfa AF: 0.443 Hom.: 31008

Bravo AF: 0.473

Asia WGS AF: 0.315 AC: 1094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.36

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: rs9364628; hg19: chr6-162339286;