rs938671

chr17-42521703-T-C

Variant summary

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

The NM_001130021.3(ATP6V0A1):c.*583T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 152,336 control chromosomes in the GnomAD database, including 435 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 0.072 (434 hom., cov: 32)
  • Exomes 𝑓: 0.052 (1 hom.)
• Consequence: ATP6V0A1 NM_001130021.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

Genes affected

ATP6V0A1 (HGNC:865): (ATPase H+ transporting V0 subunit a1) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c", and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This gene encodes one of three A subunit proteins and the encoded protein is associated with clathrin-coated vesicles. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6V0A1	NM_001130021.3	c.*583T>C		3_prime_UTR_variant	22/22	ENST00000343619.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V0A1	ENST00000343619.9	c.*583T>C		3_prime_UTR_variant	22/22	1	NM_001130021.3	P4

Frequencies

GnomAD3 genomes AF: 0.0723 AC: 10979 AN: 151928 Hom.: 433 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.0721

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0559

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.0757

GnomAD4 exome AF: 0.0517 AC: 15 AN: 290 Hom.: 1 Cov.: 0 AF XY: 0.0663 AC XY: 13 AN XY: 196

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.0588

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0373

GnomAD4 genome AF: 0.0723 AC: 10998 AN: 152046 Hom.: 434 Cov.: 32 AF XY: 0.0721 AC XY: 5361 AN XY: 74326

Gnomad4 AFR AF: 0.0694

Gnomad4 AMR AF: 0.0721

Gnomad4 ASJ AF: 0.0721

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0559

Gnomad4 NFE AF: 0.0681

Gnomad4 OTH AF: 0.0778

Alfa AF: 0.0658 Hom.: 90

Bravo AF: 0.0716

Asia WGS AF: 0.150 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.39
Dann	Benign	0.53

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: rs938671; hg19: chr17-40673721;