rs9456721

Variant names:

• chr6-161879876-A-C
• rs9456721
• NM_004562.3:c.734+93426T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-161879876-A-C
• chr6-161879876-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004562.3(PRKN):​c.734+93426T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,942 control chromosomes in the GnomAD database, including 15,336 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 0.43 (15336 hom., cov: 32)
• Consequence: PRKN NM_004562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKN	NM_004562.3	c.734+93426T>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+93426T>G		intron_variant	Intron 6 of 11	1	NM_004562.3	ENSP00000355865.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65930 AN: 151824 Hom.: 15329 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.434 AC: 65954 AN: 151942 Hom.: 15336 Cov.: 32 AF XY: 0.433 AC XY: 32135 AN XY: 74274

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.454

Alfa AF: 0.511 Hom.: 19559

Bravo AF: 0.428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	8.0
DANN	Benign	0.83

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: rs9456721; hg19: chr6-162300908;