6-162032707-C-T

Variant names:

• chr6-162032707-C-T
• rs1105056
• NM_004562.3:c.618+21384G>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.618+21384G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,084 control chromosomes in the GnomAD database, including 2,822 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 0.17 (2822 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.724
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.618+21384G>A		intron_variant	Intron 5 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.618+21384G>A		intron_variant	Intron 5 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25175 AN: 151966 Hom.: 2816 Cov.: 32

Gnomad AFR AF: 0.0692

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.166 AC: 25191 AN: 152084 Hom.: 2822 Cov.: 32 AF XY: 0.171 AC XY: 12725 AN XY: 74320

African (AFR) AF: 0.0692 AC: 2872 AN: 41522

American (AMR) AF: 0.224 AC: 3417 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 730 AN: 3470

East Asian (EAS) AF: 0.552 AC: 2835 AN: 5138

South Asian (SAS) AF: 0.233 AC: 1121 AN: 4820

European-Finnish (FIN) AF: 0.220 AC: 2323 AN: 10574

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.168 AC: 11438 AN: 67982

Other (OTH) AF: 0.163 AC: 344 AN: 2106

Alfa AF: 0.155 Hom.: 1170

Bravo AF: 0.167

Asia WGS AF: 0.383 AC: 1328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.55
DANN	Benign	0.68
PhyloP100		-0.72
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: rs1105056; hg19: chr6-162453739; COSMIC: COSV58267243;