rs9456801

Variant names:

• chr6-162607258-T-A
• rs9456801
• NM_004562.3:c.7+120404A>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.7+120404A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 151,952 control chromosomes in the GnomAD database, including 4,903 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 0.23 (4903 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.7+120404A>T		intron_variant	Intron 1 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.7+120404A>T		intron_variant	Intron 1 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35377 AN: 151834 Hom.: 4895 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.233 AC: 35409 AN: 151952 Hom.: 4903 Cov.: 32 AF XY: 0.234 AC XY: 17390 AN XY: 74266

African (AFR) AF: 0.376 AC: 15571 AN: 41404

American (AMR) AF: 0.289 AC: 4412 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 770 AN: 3466

East Asian (EAS) AF: 0.214 AC: 1102 AN: 5160

South Asian (SAS) AF: 0.208 AC: 998 AN: 4806

European-Finnish (FIN) AF: 0.156 AC: 1653 AN: 10574

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10257 AN: 67958

Other (OTH) AF: 0.209 AC: 441 AN: 2106

Alfa AF: 0.209 Hom.: 466

Bravo AF: 0.248

Asia WGS AF: 0.231 AC: 802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.69
PhyloP100		-0.15
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: rs9456801; hg19: chr6-163028290;