7-138706851-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020632.3(ATP6V0A4):c.2430-134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,423,164 control chromosomes in the GnomAD database, including 59,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (6296 hom., cov: 25)
  • Exomes 𝑓: 0.29 (52817 hom.)
• Consequence: ATP6V0A4 NM_020632.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.04

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-138706851-A-G is Benign according to our data. Variant chr7-138706851-A-G is described in ClinVar as [Benign]. Clinvar id is 1279939.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6V0A4	NM_020632.3	c.2430-134T>C		intron_variant		ENST00000310018.7
ATP6V0A4	NM_130840.3	c.2430-134T>C		intron_variant
ATP6V0A4	NM_130841.3	c.2430-134T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V0A4	ENST00000310018.7	c.2430-134T>C		intron_variant		1	NM_020632.3	P1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 42368 AN: 147496 Hom.: 6284 Cov.: 25

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.286 AC: 365042 AN: 1275600 Hom.: 52817 AF XY: 0.283 AC XY: 178162 AN XY: 630270

Gnomad4 AFR exome AF: 0.314

Gnomad4 AMR exome AF: 0.453

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.364

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.287 AC: 42407 AN: 147564 Hom.: 6296 Cov.: 25 AF XY: 0.285 AC XY: 20403 AN XY: 71516

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.265

Alfa AF: 0.273 Hom.: 1389

Bravo AF: 0.304

Asia WGS AF: 0.313 AC: 1088 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.5
Dann	Benign	0.42

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: rs12707394; hg19: chr7-138391596; COSMIC: COSV59473561; COSMIC: COSV59473561;