3-113778539-C-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.-13-202C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,052 control chromosomes in the GnomAD database, including 6,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (6952 hom., cov: 32)
• Consequence: ATP6V1A NM_001690.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.957

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 3-113778539-C-G is Benign according to our data. Variant chr3-113778539-C-G is described in ClinVar as [Benign]. Clinvar id is 1183335.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6V1A	NM_001690.4	c.-13-202C>G		intron_variant		ENST00000273398.8
ATP6V1A	XM_047448305.1	c.-13-202C>G		intron_variant
ATP6V1A	XM_047448306.1	c.-13-202C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V1A	ENST00000273398.8	c.-13-202C>G		intron_variant		1	NM_001690.4	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43350 AN: 151934 Hom.: 6955 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.285 AC: 43337 AN: 152052 Hom.: 6952 Cov.: 32 AF XY: 0.287 AC XY: 21333 AN XY: 74294

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.274

Alfa AF: 0.214 Hom.: 540

Bravo AF: 0.264

Asia WGS AF: 0.238 AC: 826 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	2.2
Dann	Benign	0.44

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: rs12631232; hg19: chr3-113497386;