NM_020632.3:c.1478+17A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020632.3(ATP6V0A4):c.1478+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,603,716 control chromosomes in the GnomAD database, including 31,139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6143 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24996 hom. )

Consequence

ATP6V0A4
NM_020632.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.210

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

renal tubular acidosis, distal, 3, with or without sensorineural hearing loss
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
autosomal recessive distal renal tubular acidosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ATP6V0A4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-138745106-T-C is Benign according to our data. Variant chr7-138745106-T-C is described in ClinVar as Benign. ClinVar VariationId is 261341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ATP6V0A4	NM_020632.3 link	c.1478+17A>G	intron_variant	Intron 14 of 21	ENST00000310018.7	NP_065683.2	Q9HBG4A0A024R791
ATP6V0A4	NM_130840.3 link	c.1478+17A>G	intron_variant	Intron 13 of 20		NP_570855.2	Q9HBG4A0A024R791
ATP6V0A4	NM_130841.3 link	c.1478+17A>G	intron_variant	Intron 13 of 20		NP_570856.2	Q9HBG4A0A024R791

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0A4	ENST00000310018.7 link	c.1478+17A>G		intron_variant	Intron 14 of 21	1	NM_020632.3	ENSP00000308122.2		Q9HBG4

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38620

AN:

152068

Hom.:

6116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.452

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.231

GnomAD2 exomes

AF:

0.189

AC:

47469

AN:

251436

AF XY:

0.183

show subpopulations

Gnomad AFR exome

AF:

0.460

Gnomad AMR exome

AF:

0.102

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.288

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.178

Gnomad OTH exome

AF:

0.190

GnomAD4 exome

AF:

0.177

AC:

256840

AN:

1451530

Hom.:

24996

Cov.:

AF XY:

0.176

AC XY:

126863

AN XY:

722798

show subpopulations

African (AFR)

AF:

0.471

AC:

15626

AN:

33196

American (AMR)

AF:

0.107

AC:

4801

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

4833

AN:

26082

East Asian (EAS)

AF:

0.258

AC:

10240

AN:

39628

South Asian (SAS)

AF:

0.133

AC:

11416

AN:

86036

European-Finnish (FIN)

AF:

0.170

AC:

9072

AN:

53404

Middle Eastern (MID)

AF:

0.204

AC:

1167

AN:

5720

European-Non Finnish (NFE)

AF:

0.170

AC:

187722

AN:

1102682

Other (OTH)

AF:

0.199

AC:

11963

AN:

60084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

10490

20980

31471

41961

52451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6644

13288

19932

26576

33220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.254

AC:

38687

AN:

152186

Hom.:

6143

Cov.:

AF XY:

0.251

AC XY:

18690

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.453

AC:

18777

AN:

41490

American (AMR)

AF:

0.160

AC:

2443

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

614

AN:

3472

East Asian (EAS)

AF:

0.275

AC:

1425

AN:

5184

South Asian (SAS)

AF:

0.139

AC:

673

AN:

4826

European-Finnish (FIN)

AF:

0.181

AC:

1918

AN:

10596

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.178

AC:

12083

AN:

68010

Other (OTH)

AF:

0.232

AC:

491

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1407

2815

4222

5630

7037

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

372

744

1116

1488

1860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.207

Hom.:

8130

Bravo

AF:

0.265

Asia WGS

AF:

0.247

AC:

857

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal recessive distal renal tubular acidosis

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.7

(source)

DANN

Benign

0.45

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over