chr6-161961702-A-G

Position:

• chr6-161961702-A-G

Variant summary

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

The NM_004562.3(PRKN):​c.734+11600T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,930 control chromosomes in the GnomAD database, including 12,150 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 0.40 (12150 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKN	NM_004562.3	c.734+11600T>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.734+11600T>C		intron_variant		1	NM_004562.3	ENSP00000355865	P1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60295 AN: 151812 Hom.: 12141 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.397 AC: 60329 AN: 151930 Hom.: 12150 Cov.: 32 AF XY: 0.403 AC XY: 29884 AN XY: 74224

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.389

Alfa AF: 0.412 Hom.: 17316

Bravo AF: 0.385

Asia WGS AF: 0.430 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.28

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: rs1784594; hg19: chr6-162382734;