6-161580404-T-C

Variant names:

• chr6-161580404-T-C
• rs992037
• NM_004562.3:c.872-10988A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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 -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 rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.872-10988A>G		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.872-10988A>G		intron_variant	Intron 7 of 11	1	NM_004562.3	ENSP00000355865.1

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

African (AFR) AF: 0.884 AC: 36687 AN: 41494

American (AMR) AF: 0.569 AC: 8692 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2610 AN: 3472

East Asian (EAS) AF: 0.710 AC: 3669 AN: 5164

South Asian (SAS) AF: 0.611 AC: 2944 AN: 4818

European-Finnish (FIN) AF: 0.712 AC: 7536 AN: 10586

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42401 AN: 67948

Other (OTH) AF: 0.689 AC: 1450 AN: 2106

Alfa AF: 0.650 Hom.: 33815

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
PhyloP100		-0.44
Mutation Taster		=100/0	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: rs992037; hg19: chr6-162001436; COSMIC: COSV58266179;