6-161771962-G-T

Variant names:

• chr6-161771962-G-T
• rs9458363
• NM_004562.3:c.871+13810C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004562.3(PRKN):​c.871+13810C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,976 control chromosomes in the GnomAD database, including 11,396 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 0.39 (11396 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 4 publications found

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]

PRKN Gene-Disease associations (from GenCC):

• autosomal recessive juvenile Parkinson disease 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp
• Parkinson disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• young-onset Parkinson disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.871+13810C>A		intron_variant	Intron 7 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.871+13810C>A		intron_variant	Intron 7 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58531 AN: 151856 Hom.: 11364 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.386 AC: 58600 AN: 151976 Hom.: 11396 Cov.: 32 AF XY: 0.384 AC XY: 28495 AN XY: 74290

African (AFR) AF: 0.427 AC: 17664 AN: 41408

American (AMR) AF: 0.303 AC: 4624 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1582 AN: 3466

East Asian (EAS) AF: 0.385 AC: 1988 AN: 5162

South Asian (SAS) AF: 0.517 AC: 2494 AN: 4824

European-Finnish (FIN) AF: 0.300 AC: 3172 AN: 10556

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25878 AN: 67966

Other (OTH) AF: 0.384 AC: 812 AN: 2114

Alfa AF: 0.378 Hom.: 2183

Bravo AF: 0.383

Asia WGS AF: 0.459 AC: 1595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.75
PhyloP100		1.7
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9458363; hg19: chr6-162192994; COSMIC: COSV58210559;