rs3807154

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020632.3(ATP6V0A4):c.1812T>C(p.His604His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 1,613,270 control chromosomes in the GnomAD database, including 410,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 34209 hom., cov: 30)

Exomes 𝑓: 0.72 ( 376173 hom. )

Consequence

ATP6V0A4
NM_020632.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0700

Variant links:

Genes affected

ATP6V0A4 (HGNC:866): (ATPase H+ transporting V0 subunit a4) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent 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. This gene is one of four genes in man and mouse that encode different isoforms of the a subunit. Alternatively spliced transcript variants encoding the same protein have been described. Mutations in this gene are associated with renal tubular acidosis associated with preserved hearing. [provided by RefSeq, Jul 2008]

ATP6V0A4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 7-138732973-A-G is Benign according to our data. Variant chr7-138732973-A-G is described in ClinVar as [Benign]. Clinvar id is 261343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-138732973-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V0A4	NM_020632.3 link	c.1812T>C	p.His604His	synonymous_variant	Exon 17 of 22	ENST00000310018.7	NP_065683.2	Q9HBG4A0A024R791
ATP6V0A4	NM_130840.3 link	c.1812T>C	p.His604His	synonymous_variant	Exon 16 of 21		NP_570855.2	Q9HBG4A0A024R791
ATP6V0A4	NM_130841.3 link	c.1812T>C	p.His604His	synonymous_variant	Exon 16 of 21		NP_570856.2	Q9HBG4A0A024R791

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0A4	ENST00000310018.7 link	c.1812T>C	p.His604His	synonymous_variant	Exon 17 of 22	1	NM_020632.3	ENSP00000308122.2		Q9HBG4

Frequencies

GnomAD3 genomes

AF:

0.660

AC:

100206

AN:

151724

Hom.:

34202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.799

Gnomad AMR

AF:

0.759

Gnomad ASJ

AF:

0.690

Gnomad EAS

AF:

0.812

Gnomad SAS

AF:

0.738

Gnomad FIN

AF:

0.768

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.717

Gnomad OTH

AF:

0.655

GnomAD3 exomes

AF:

0.729

AC:

183187

AN:

251388

Hom.:

67755

AF XY:

0.730

AC XY:

99185

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.457

Gnomad AMR exome

AF:

0.830

Gnomad ASJ exome

AF:

0.696

Gnomad EAS exome

AF:

0.822

Gnomad SAS exome

AF:

0.736

Gnomad FIN exome

AF:

0.763

Gnomad NFE exome

AF:

0.716

Gnomad OTH exome

AF:

0.730

GnomAD4 exome

AF:

0.715

AC:

1045437

AN:

1461428

Hom.:

376173

Cov.:

AF XY:

0.717

AC XY:

521051

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.465

Gnomad4 AMR exome

AF:

0.822

Gnomad4 ASJ exome

AF:

0.691

Gnomad4 EAS exome

AF:

0.795

Gnomad4 SAS exome

AF:

0.734

Gnomad4 FIN exome

AF:

0.763

Gnomad4 NFE exome

AF:

0.713

Gnomad4 OTH exome

AF:

0.709

GnomAD4 genome

AF:

0.660

AC:

100240

AN:

151842

Hom.:

34209

Cov.:

AF XY:

0.665

AC XY:

49374

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.470

Gnomad4 AMR

AF:

0.759

Gnomad4 ASJ

AF:

0.690

Gnomad4 EAS

AF:

0.812

Gnomad4 SAS

AF:

0.739

Gnomad4 FIN

AF:

0.768

Gnomad4 NFE

AF:

0.717

Gnomad4 OTH

AF:

0.651

Alfa

AF:

0.702

Hom.:

52487

Bravo

AF:

0.653

Asia WGS

AF:

0.731

AC:

2541

AN:

3478

EpiCase

AF:

0.719

EpiControl

AF:

0.727

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive distal renal tubular acidosis

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.093

DANN

Benign

0.36

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