rs3019449

Variant names:

• chr6-161744061-A-C
• rs3019449
• NM_004562.3:c.871+41711T>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.871+41711T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 151,992 control chromosomes in the GnomAD database, including 38,519 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 0.71 (38519 hom., cov: 31)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.785
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.871+41711T>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.871+41711T>G		intron_variant	Intron 7 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107651 AN: 151874 Hom.: 38484 Cov.: 31

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.709 AC: 107744 AN: 151992 Hom.: 38519 Cov.: 31 AF XY: 0.711 AC XY: 52826 AN XY: 74272

African (AFR) AF: 0.748 AC: 31021 AN: 41448

American (AMR) AF: 0.676 AC: 10332 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2423 AN: 3468

East Asian (EAS) AF: 0.921 AC: 4747 AN: 5152

South Asian (SAS) AF: 0.821 AC: 3945 AN: 4804

European-Finnish (FIN) AF: 0.630 AC: 6644 AN: 10550

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46336 AN: 67976

Other (OTH) AF: 0.715 AC: 1508 AN: 2110

Alfa AF: 0.690 Hom.: 6338

Bravo AF: 0.710

Asia WGS AF: 0.846 AC: 2940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.38
DANN	Benign	0.52
PhyloP100		-0.79
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: rs3019449; hg19: chr6-162165093;