chr6-161727303-T-C

Variant names:

• chr6-161727303-T-C
• rs6455767
• NM_004562.3:c.871+58469A>G

Variant summary

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

The NM_004562.3(PRKN):​c.871+58469A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,122 control chromosomes in the GnomAD database, including 11,464 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 0.26 (11464 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• 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 = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.871+58469A>G		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.871+58469A>G		intron_variant	Intron 7 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39038 AN: 152004 Hom.: 11424 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0678

Gnomad EAS AF: 0.0367

Gnomad SAS AF: 0.0843

Gnomad FIN AF: 0.0496

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0825

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.257 AC: 39132 AN: 152122 Hom.: 11464 Cov.: 32 AF XY: 0.248 AC XY: 18474 AN XY: 74388

African (AFR) AF: 0.724 AC: 30027 AN: 41448

American (AMR) AF: 0.107 AC: 1629 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0678 AC: 235 AN: 3464

East Asian (EAS) AF: 0.0366 AC: 189 AN: 5170

South Asian (SAS) AF: 0.0835 AC: 403 AN: 4824

European-Finnish (FIN) AF: 0.0496 AC: 527 AN: 10618

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0825 AC: 5610 AN: 67986

Other (OTH) AF: 0.198 AC: 419 AN: 2114

Alfa AF: 0.129 Hom.: 7497

Bravo AF: 0.280

Asia WGS AF: 0.130 AC: 454 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	3.4
DANN	Benign	0.58
PhyloP100		-0.16
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: rs6455767; hg19: chr6-162148335;