6-161961702-A-G

Variant names:

• chr6-161961702-A-G
• rs1784594
• NM_004562.3:c.734+11600T>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.734+11600T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,930 control chromosomes in the GnomAD database, including 12,150 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 0.40 (12150 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 10 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 (SAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.734+11600T>C		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+11600T>C		intron_variant	Intron 6 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60295 AN: 151812 Hom.: 12141 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.397 AC: 60329 AN: 151930 Hom.: 12150 Cov.: 32 AF XY: 0.403 AC XY: 29884 AN XY: 74224

African (AFR) AF: 0.349 AC: 14461 AN: 41440

American (AMR) AF: 0.369 AC: 5631 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1405 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2191 AN: 5156

South Asian (SAS) AF: 0.510 AC: 2451 AN: 4804

European-Finnish (FIN) AF: 0.433 AC: 4562 AN: 10542

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.415 AC: 28212 AN: 67954

Other (OTH) AF: 0.389 AC: 820 AN: 2108

Alfa AF: 0.408 Hom.: 21595

Bravo AF: 0.385

Asia WGS AF: 0.430 AC: 1492 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	0.77
DANN	Benign	0.28
PhyloP100		-0.39
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: rs1784594; hg19: chr6-162382734;