Variant 3-113780886-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.692

Variant links:

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]

ATP6V1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ATP6V1A	NM_001690.4 linkuse as main transcript	c.83-164A>G	intron_variant	ENST00000273398.8
ATP6V1A	XM_047448305.1 linkuse as main transcript	c.83-164A>G	intron_variant
ATP6V1A	XM_047448306.1 linkuse as main transcript	c.83-164A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V1A	ENST00000273398.8 linkuse as main transcript	c.83-164A>G		intron_variant		1	NM_001690.4	P1	P38606-1

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

53910

AN:

151926

Hom.:

9685

Cov.:

show subpopulations

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.:

AF XY:

0.337

AC XY:

188558

AN XY:

559066

show subpopulations

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.:

AF XY:

0.355

AC XY:

26417

AN XY:

74352

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over