6-162718148-T-G

Position:

• chr6-162718148-T-G

Variant summary

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

The NM_004562.3(PRKN):​c.7+9514A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,848 control chromosomes in the GnomAD database, including 10,464 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 0.37 (10464 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKN	NM_004562.3	c.7+9514A>C		intron_variant		ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.7+9514A>C		intron_variant		1	NM_004562.3	ENSP00000355865	P1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55801 AN: 151730 Hom.: 10457 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.368 AC: 55836 AN: 151848 Hom.: 10464 Cov.: 32 AF XY: 0.360 AC XY: 26687 AN XY: 74212

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.387

Alfa AF: 0.272 Hom.: 784

Bravo AF: 0.373

Asia WGS AF: 0.256 AC: 892 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs2803104; hg19: chr6-163139180; COSMIC: COSV58269986;