rs13191362

Variant names:

• chr6-162612318-A-G
• rs13191362
• NM_004562.3:c.7+115344T>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.7+115344T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 152,134 control chromosomes in the GnomAD database, including 724 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 0.087 (724 hom., cov: 30)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750
• Publications: 88 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.7+115344T>C		intron_variant	Intron 1 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.7+115344T>C		intron_variant	Intron 1 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.0871 AC: 13240 AN: 152020 Hom.: 722 Cov.: 30

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.0928

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.0871 AC: 13247 AN: 152134 Hom.: 724 Cov.: 30 AF XY: 0.0847 AC XY: 6296 AN XY: 74372

African (AFR) AF: 0.0509 AC: 2114 AN: 41526

American (AMR) AF: 0.0939 AC: 1434 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0928 AC: 322 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5180

South Asian (SAS) AF: 0.0825 AC: 398 AN: 4822

European-Finnish (FIN) AF: 0.0548 AC: 579 AN: 10566

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7957 AN: 67978

Other (OTH) AF: 0.110 AC: 233 AN: 2112

Alfa AF: 0.108 Hom.: 1648

Bravo AF: 0.0886

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.72
PhyloP100		0.75
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: rs13191362; hg19: chr6-163033350;