6-162546064-T-C

Variant names:

• chr6-162546064-T-C
• rs6930532
• NM_004562.3:c.8-102591A>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.8-102591A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 150,666 control chromosomes in the GnomAD database, including 6,148 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 0.25 (6148 hom., cov: 31)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.8-102591A>G		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.8-102591A>G		intron_variant	Intron 1 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 37956 AN: 150570 Hom.: 6143 Cov.: 31

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.252 AC: 37977 AN: 150666 Hom.: 6148 Cov.: 31 AF XY: 0.250 AC XY: 18383 AN XY: 73518

African (AFR) AF: 0.460 AC: 18684 AN: 40652

American (AMR) AF: 0.228 AC: 3434 AN: 15088

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3466

East Asian (EAS) AF: 0.213 AC: 1094 AN: 5136

South Asian (SAS) AF: 0.210 AC: 1008 AN: 4800

European-Finnish (FIN) AF: 0.152 AC: 1559 AN: 10290

Middle Eastern (MID) AF: 0.203 AC: 59 AN: 290

European-Non Finnish (NFE) AF: 0.157 AC: 10647 AN: 67934

Other (OTH) AF: 0.221 AC: 465 AN: 2102

Alfa AF: 0.160 Hom.: 1656

Bravo AF: 0.268

Asia WGS AF: 0.241 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.85
PhyloP100		0.34
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: rs6930532; hg19: chr6-162967096;