3-113780886-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001690.4(ATP6V1A):c.83-164A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,278,866 control chromosomes in the GnomAD database, including 77,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (9698 hom., cov: 32)
  • Exomes 𝑓: 0.34 (67562 hom.)
• Consequence: ATP6V1A NM_001690.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.692

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 3-113780886-A-G is Benign according to our data. Variant chr3-113780886-A-G is described in ClinVar as [Benign]. Clinvar id is 1228236.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	UniProt
ATP6V1A	NM_001690.4	c.83-164A>G		intron_variant		ENST00000273398.8
ATP6V1A	XM_047448305.1	c.83-164A>G		intron_variant
ATP6V1A	XM_047448306.1	c.83-164A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V1A	ENST00000273398.8	c.83-164A>G		intron_variant		1	NM_001690.4	P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53910 AN: 151926 Hom.: 9685 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.340 AC: 383503 AN: 1126822 Hom.: 67562 Cov.: 14 AF XY: 0.337 AC XY: 188558 AN XY: 559066

Gnomad4 AFR exome AF: 0.384

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.347

Gnomad4 OTH exome AF: 0.327

GnomAD4 genome AF: 0.355 AC: 53949 AN: 152044 Hom.: 9698 Cov.: 32 AF XY: 0.355 AC XY: 26417 AN XY: 74352

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.326

Alfa AF: 0.358 Hom.: 1222

Bravo AF: 0.343

Asia WGS AF: 0.262 AC: 908 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	9.8
Dann	Benign	0.71

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: rs2305545; hg19: chr3-113499733; COSMIC: COSV56362327; COSMIC: COSV56362327;