3-113811364-T-C

Position:

• chr3-113811364-T-C

Variant summary

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

The NM_001690.4(ATP6V1A):​c.*1937T>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 0.354 in 152,440 control chromosomes in the GnomAD database, including 9,709 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 0.35 (9661 hom., cov: 32)
  • Exomes 𝑓: 0.48 (48 hom.)
• Consequence: ATP6V1A NM_001690.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530

Genes affected

ATP6V1A (HGNC:851): (ATPase H+ transporting V1 subunit A) 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 encoded protein is one of two V1 domain A subunit isoforms and is found in all tissues. Transcript variants derived from alternative polyadenylation exist. [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 (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V1A	NM_001690.4	c.*1937T>C		3_prime_UTR_variant	15/15	ENST00000273398.8	NP_001681.2
ATP6V1A	XM_047448305.1	c.*1937T>C		3_prime_UTR_variant	15/15		XP_047304261.1
ATP6V1A	XM_047448306.1	c.*1937T>C		3_prime_UTR_variant	16/16		XP_047304262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V1A	ENST00000273398.8	c.*1937T>C		3_prime_UTR_variant	15/15	1	NM_001690.4	ENSP00000273398	P1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53762 AN: 151888 Hom.: 9648 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.477 AC: 207 AN: 434 Hom.: 48 Cov.: 0 AF XY: 0.454 AC XY: 119 AN XY: 262

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.833

GnomAD4 genome AF: 0.354 AC: 53804 AN: 152006 Hom.: 9661 Cov.: 32 AF XY: 0.354 AC XY: 26288 AN XY: 74290

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.327

Alfa AF: 0.355 Hom.: 2448

Bravo AF: 0.343

Asia WGS AF: 0.253 AC: 876 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	2.0
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: rs12736; hg19: chr3-113530211; COSMIC: COSV56364331; COSMIC: COSV56364331;