rs992421

chr6-161494950-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.1083+53904G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,014 control chromosomes in the GnomAD database, including 22,732 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 0.52 (22732 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKN	NM_004562.3	c.1083+53904G>A		intron_variant		ENST00000366898.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKN	ENST00000366898.6	c.1083+53904G>A		intron_variant		1	NM_004562.3	P1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78833 AN: 151896 Hom.: 22691 Cov.: 32

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.519 AC: 78927 AN: 152014 Hom.: 22732 Cov.: 32 AF XY: 0.508 AC XY: 37767 AN XY: 74292

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.506

Alfa AF: 0.481 Hom.: 3197

Bravo AF: 0.535

Asia WGS AF: 0.279 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.16
Dann	Benign	0.64

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: rs992421; hg19: chr6-161915982; COSMIC: COSV58264915;