rs12191995

Variant names:

• chr6-161498182-T-C
• rs12191995
• NM_004562.3:c.1083+50672A>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.1083+50672A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,222 control chromosomes in the GnomAD database, including 2,446 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 (2446 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.1083+50672A>G		intron_variant	Intron 9 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.1083+50672A>G		intron_variant	Intron 9 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25110 AN: 152104 Hom.: 2448 Cov.: 32

Gnomad AFR AF: 0.0972

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0733

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.165 AC: 25119 AN: 152222 Hom.: 2446 Cov.: 32 AF XY: 0.159 AC XY: 11810 AN XY: 74434

African (AFR) AF: 0.0973 AC: 4041 AN: 41550

American (AMR) AF: 0.163 AC: 2493 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 770 AN: 3468

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5188

South Asian (SAS) AF: 0.0728 AC: 351 AN: 4824

European-Finnish (FIN) AF: 0.153 AC: 1620 AN: 10604

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15197 AN: 67988

Other (OTH) AF: 0.198 AC: 417 AN: 2110

Alfa AF: 0.191 Hom.: 671

Bravo AF: 0.165

Asia WGS AF: 0.0590 AC: 205 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	1.5
DANN	Benign	0.49
PhyloP100		0.22
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: rs12191995; hg19: chr6-161919214;