6-161938303-A-C

Variant names:

• chr6-161938303-A-C
• rs7759273
• NM_004562.3:c.734+34999T>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+34999T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,018 control chromosomes in the GnomAD database, including 10,247 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 0.36 (10247 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

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 (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.734+34999T>G		intron_variant	Intron 6 of 11	ENST00000366898.6	NP_004553.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKN	ENST00000366898.6	c.734+34999T>G		intron_variant	Intron 6 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54905 AN: 151898 Hom.: 10243 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.361 AC: 54941 AN: 152018 Hom.: 10247 Cov.: 32 AF XY: 0.359 AC XY: 26706 AN XY: 74312

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.372

Alfa AF: 0.330 Hom.: 2740

Bravo AF: 0.352

Asia WGS AF: 0.180 AC: 626 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	1.1
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7759273; hg19: chr6-162359335;