7-138706889-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020632.3(ATP6V0A4):c.2430-173_2430-172insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0736 in 211,554 control chromosomes in the GnomAD database, including 741 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.093 (741 hom., cov: 0)
  • Exomes 𝑓: 0.058 (0 hom.)
• Consequence: ATP6V0A4 NM_020632.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.299

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 -10 ACMG points.

• BP6: Variant 7-138706889-A-AT is Benign according to our data. Variant chr7-138706889-A-AT is described in ClinVar as [Benign]. Clinvar id is 1240870.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6V0A4	NM_020632.3	c.2430-173_2430-172insA		intron_variant		ENST00000310018.7
ATP6V0A4	NM_130840.3	c.2430-173_2430-172insA		intron_variant
ATP6V0A4	NM_130841.3	c.2430-173_2430-172insA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V0A4	ENST00000310018.7	c.2430-173_2430-172insA		intron_variant		1	NM_020632.3	P1

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 8891 AN: 95532 Hom.: 742 Cov.: 0

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0986

Gnomad AMR AF: 0.0619

Gnomad ASJ AF: 0.0803

Gnomad EAS AF: 0.0401

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0201

Gnomad MID AF: 0.0714

Gnomad NFE AF: 0.0559

Gnomad OTH AF: 0.0924

GnomAD4 exome AF: 0.0577 AC: 6690 AN: 116042 Hom.: 0 AF XY: 0.0573 AC XY: 3186 AN XY: 55554

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.0351

Gnomad4 ASJ exome AF: 0.0789

Gnomad4 EAS exome AF: 0.0528

Gnomad4 SAS exome AF: 0.0943

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.0558

Gnomad4 OTH exome AF: 0.0631

GnomAD4 genome AF: 0.0930 AC: 8884 AN: 95512 Hom.: 741 Cov.: 0 AF XY: 0.0936 AC XY: 4093 AN XY: 43720

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.0618

Gnomad4 ASJ AF: 0.0803

Gnomad4 EAS AF: 0.0396

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0201

Gnomad4 NFE AF: 0.0558

Gnomad4 OTH AF: 0.0926

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

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs11308035; hg19: chr7-138391634;