chr6-162086658-A-G

Position:

• chr6-162086658-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.535-32484T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,140 control chromosomes in the GnomAD database, including 45,220 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 0.77 (45220 hom., cov: 33)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKN	NM_004562.3	c.535-32484T>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.535-32484T>C		intron_variant		1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116603 AN: 152022 Hom.: 45175 Cov.: 33

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.767 AC: 116702 AN: 152140 Hom.: 45220 Cov.: 33 AF XY: 0.768 AC XY: 57119 AN XY: 74372

Gnomad4 AFR AF: 0.883

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.860

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.731

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.751

Alfa AF: 0.720 Hom.: 52898

Bravo AF: 0.775

Asia WGS AF: 0.814 AC: 2828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.14
DANN	Benign	0.52

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: rs1893551; hg19: chr6-162507690;