6-162049864-C-T

Variant names:

• chr6-162049864-C-T
• rs2023048
• NM_004562.3:c.618+4227G>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+4227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 152,148 control chromosomes in the GnomAD database, including 56,310 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 0.86 (56310 hom., cov: 31)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.618+4227G>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+4227G>A		intron_variant	Intron 5 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130714 AN: 152030 Hom.: 56265 Cov.: 31

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.868

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

GnomAD4 genome AF: 0.860 AC: 130815 AN: 152148 Hom.: 56310 Cov.: 31 AF XY: 0.860 AC XY: 63976 AN XY: 74386

African (AFR) AF: 0.867 AC: 35986 AN: 41508

American (AMR) AF: 0.903 AC: 13808 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3026 AN: 3470

East Asian (EAS) AF: 0.873 AC: 4511 AN: 5166

South Asian (SAS) AF: 0.794 AC: 3821 AN: 4812

European-Finnish (FIN) AF: 0.873 AC: 9232 AN: 10570

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57549 AN: 68022

Other (OTH) AF: 0.868 AC: 1830 AN: 2108

Alfa AF: 0.852 Hom.: 94345

Bravo AF: 0.864

Asia WGS AF: 0.843 AC: 2930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.20
DANN	Benign	0.66
PhyloP100		-0.48
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: rs2023048; hg19: chr6-162470896;