6-161478248-G-A

Variant names:

• chr6-161478248-G-A
• rs9458281
• NM_004562.3:c.1083+70606C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004562.3(PRKN):​c.1083+70606C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,132 control chromosomes in the GnomAD database, including 3,680 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 0.20 (3680 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• 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

LOC105378098 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.1083+70606C>T		intron_variant	Intron 9 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.1083+70606C>T		intron_variant	Intron 9 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31010 AN: 152014 Hom.: 3670 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.204 AC: 31065 AN: 152132 Hom.: 3680 Cov.: 32 AF XY: 0.201 AC XY: 14977 AN XY: 74364

African (AFR) AF: 0.329 AC: 13628 AN: 41474

American (AMR) AF: 0.160 AC: 2443 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 615 AN: 3472

East Asian (EAS) AF: 0.140 AC: 725 AN: 5170

South Asian (SAS) AF: 0.177 AC: 853 AN: 4822

European-Finnish (FIN) AF: 0.176 AC: 1867 AN: 10588

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10368 AN: 67994

Other (OTH) AF: 0.196 AC: 414 AN: 2114

Alfa AF: 0.138 Hom.: 454

Bravo AF: 0.210

Asia WGS AF: 0.173 AC: 601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
DANN	Benign	0.59
PhyloP100		-0.36
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: rs9458281; hg19: chr6-161899280;