7-138749740-T-C

Position:

• chr7-138749740-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020632.3(ATP6V0A4):​c.1030-423A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 151,832 control chromosomes in the GnomAD database, including 36,896 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 0.69 (36896 hom., cov: 30)
• Consequence: ATP6V0A4 NM_020632.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V0A4	NM_020632.3	c.1030-423A>G		intron_variant		ENST00000310018.7	NP_065683.2
ATP6V0A4	NM_130840.3	c.1030-423A>G		intron_variant			NP_570855.2
ATP6V0A4	NM_130841.3	c.1030-423A>G		intron_variant			NP_570856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V0A4	ENST00000310018.7	c.1030-423A>G		intron_variant		1	NM_020632.3	ENSP00000308122.2

Frequencies

GnomAD3 genomes AF: 0.685 AC: 103969 AN: 151714 Hom.: 36838 Cov.: 30

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.686 AC: 104087 AN: 151832 Hom.: 36896 Cov.: 30 AF XY: 0.679 AC XY: 50344 AN XY: 74184

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.645

Alfa AF: 0.615 Hom.: 50793

Bravo AF: 0.699

Asia WGS AF: 0.555 AC: 1929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	10
DANN	Benign	0.85

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: rs366193; hg19: chr7-138434485;