7-138726680-C-T

Variant names:

• chr7-138726680-C-T
• rs3800569
• NM_020632.3:c.2010+2081G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020632.3(ATP6V0A4):​c.2010+2081G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,132 control chromosomes in the GnomAD database, including 46,439 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (46439 hom., cov: 31)
• Consequence: ATP6V0A4 NM_020632.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 11 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020632.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0A4	NM_020632.3	MANE Select	c.2010+2081G>A		intron	N/A	NP_065683.2
	ATP6V0A4	NM_130840.3		c.2010+2081G>A		intron	N/A	NP_570855.2
	ATP6V0A4	NM_130841.3		c.2010+2081G>A		intron	N/A	NP_570856.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0A4	ENST00000310018.7	TSL:1 MANE Select	c.2010+2081G>A		intron	N/A	ENSP00000308122.2
	ATP6V0A4	ENST00000353492.4	TSL:1	c.2010+2081G>A		intron	N/A	ENSP00000253856.6
	ATP6V0A4	ENST00000393054.5	TSL:5	c.2010+2081G>A		intron	N/A	ENSP00000376774.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118498 AN: 152012 Hom.: 46396 Cov.: 31

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.780 AC: 118596 AN: 152132 Hom.: 46439 Cov.: 31 AF XY: 0.781 AC XY: 58055 AN XY: 74368

African (AFR) AF: 0.851 AC: 35317 AN: 41520

American (AMR) AF: 0.794 AC: 12130 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2366 AN: 3472

East Asian (EAS) AF: 0.801 AC: 4111 AN: 5134

South Asian (SAS) AF: 0.799 AC: 3849 AN: 4816

European-Finnish (FIN) AF: 0.758 AC: 8038 AN: 10598

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.739 AC: 50268 AN: 67994

Other (OTH) AF: 0.761 AC: 1605 AN: 2110

Alfa AF: 0.752 Hom.: 183503

Bravo AF: 0.784

Asia WGS AF: 0.798 AC: 2775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.62
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3800569; hg19: chr7-138411425;