rs9295184

Positions:

• chr6-162188687-G-C
• chr6-162188687-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004562.3(PRKN):​c.534+12444C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 149,856 control chromosomes in the GnomAD database, including 9,092 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 0.33 (9092 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKN	NM_004562.3	c.534+12444C>G		intron_variant		ENST00000366898.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKN	ENST00000366898.6	c.534+12444C>G		intron_variant		1	NM_004562.3	P1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 49809 AN: 149760 Hom.: 9101 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.332 AC: 49798 AN: 149856 Hom.: 9092 Cov.: 32 AF XY: 0.331 AC XY: 24208 AN XY: 73192

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.340

Alfa AF: 0.364 Hom.: 1325

Bravo AF: 0.311

Asia WGS AF: 0.327 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9295184; hg19: chr6-162609719;