6-162513112-C-T

Position:

• chr6-162513112-C-T

Variant summary

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

The ENST00000366898.6(PRKN):​c.8-69639G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 152,058 control chromosomes in the GnomAD database, including 595 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 0.085 (595 hom., cov: 32)
• Consequence: PRKN ENST00000366898.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKN	NM_004562.3	c.8-69639G>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.8-69639G>A		intron_variant		1	NM_004562.3	ENSP00000355865	P1

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12916 AN: 151940 Hom.: 595 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0736

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.0423

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.0761

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

GnomAD4 genome AF: 0.0850 AC: 12919 AN: 152058 Hom.: 595 Cov.: 32 AF XY: 0.0849 AC XY: 6313 AN XY: 74332

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0735

Gnomad4 ASJ AF: 0.0885

Gnomad4 EAS AF: 0.0418

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.0589

Gnomad4 NFE AF: 0.0747

Gnomad4 OTH AF: 0.0782

Alfa AF: 0.0762 Hom.: 484

Bravo AF: 0.0850

Asia WGS AF: 0.115 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.53

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: rs7764218; hg19: chr6-162934144;