6-161580404-T-C

Variant summary

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

The NM_004562.3(PRKN):c.872-10988A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,076 control chromosomes in the GnomAD database, including 38,618 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 0.70 (38618 hom., cov: 31)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKN	NM_004562.3	c.872-10988A>G		intron_variant		ENST00000366898.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKN	ENST00000366898.6	c.872-10988A>G		intron_variant		1	NM_004562.3	P1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106677 AN: 151958 Hom.: 38577 Cov.: 31

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.702 AC: 106770 AN: 152076 Hom.: 38618 Cov.: 31 AF XY: 0.702 AC XY: 52215 AN XY: 74346

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.689

Alfa AF: 0.646 Hom.: 22000

Bravo AF: 0.697

Asia WGS AF: 0.670 AC: 2335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.1
Dann	Benign	0.45

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: rs992037; hg19: chr6-162001436; COSMIC: COSV58266179;