6-161884370-C-T

Variant names:

• chr6-161884370-C-T
• rs9347553
• NM_004562.3:c.734+88932G>A

Variant summary

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

The NM_004562.3(PRKN):​c.734+88932G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,080 control chromosomes in the GnomAD database, including 20,167 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 0.50 (20167 hom., cov: 33)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 2 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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.734+88932G>A		intron_variant	Intron 6 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.734+88932G>A		intron_variant	Intron 6 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76374 AN: 151960 Hom.: 20124 Cov.: 33

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.503 AC: 76475 AN: 152080 Hom.: 20167 Cov.: 33 AF XY: 0.507 AC XY: 37646 AN XY: 74324

African (AFR) AF: 0.667 AC: 27660 AN: 41482

American (AMR) AF: 0.476 AC: 7271 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1496 AN: 3470

East Asian (EAS) AF: 0.587 AC: 3032 AN: 5164

South Asian (SAS) AF: 0.515 AC: 2479 AN: 4816

European-Finnish (FIN) AF: 0.476 AC: 5028 AN: 10556

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 28025 AN: 67998

Other (OTH) AF: 0.473 AC: 1000 AN: 2116

Alfa AF: 0.435 Hom.: 61063

Bravo AF: 0.506

Asia WGS AF: 0.527 AC: 1829 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.9
DANN	Benign	0.72
PhyloP100		-1.2
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: rs9347553; hg19: chr6-162305402; COSMIC: COSV58210773;