rs10945765

Variant names:

• chr6-161647533-T-G
• rs10945765
• NM_004562.3:c.872-78117A>C

Variant summary

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

The NM_004562.3(PRKN):​c.872-78117A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,910 control chromosomes in the GnomAD database, including 21,918 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 (21918 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.872-78117A>C		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.872-78117A>C		intron_variant	Intron 7 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75878 AN: 151792 Hom.: 21878 Cov.: 32

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.500 AC: 75983 AN: 151910 Hom.: 21918 Cov.: 32 AF XY: 0.490 AC XY: 36388 AN XY: 74216

African (AFR) AF: 0.809 AC: 33510 AN: 41440

American (AMR) AF: 0.305 AC: 4654 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1278 AN: 3468

East Asian (EAS) AF: 0.254 AC: 1308 AN: 5154

South Asian (SAS) AF: 0.308 AC: 1487 AN: 4824

European-Finnish (FIN) AF: 0.393 AC: 4125 AN: 10504

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28196 AN: 67926

Other (OTH) AF: 0.453 AC: 955 AN: 2110

Alfa AF: 0.433 Hom.: 57348

Bravo AF: 0.505

Asia WGS AF: 0.341 AC: 1187 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	0.63
DANN	Benign	0.76
PhyloP100		0.019
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: rs10945765; hg19: chr6-162068565;