6-161815043-C-T

Position:

• chr6-161815043-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.735-29135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,158 control chromosomes in the GnomAD database, including 61,459 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 0.90 (61459 hom., cov: 31)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

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 (AMR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKN	NM_004562.3	c.735-29135G>A		intron_variant		ENST00000366898.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKN	ENST00000366898.6	c.735-29135G>A		intron_variant		1	NM_004562.3	P1

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136558 AN: 152040 Hom.: 61427 Cov.: 31

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.885

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

GnomAD4 genome AF: 0.898 AC: 136642 AN: 152158 Hom.: 61459 Cov.: 31 AF XY: 0.894 AC XY: 66506 AN XY: 74376

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.923

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.893

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.865

Gnomad4 NFE AF: 0.895

Gnomad4 OTH AF: 0.879

Alfa AF: 0.891 Hom.: 134853

Bravo AF: 0.906

Asia WGS AF: 0.814 AC: 2834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.70

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: rs3016539; hg19: chr6-162236075;