7-138706876-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_020632.3(ATP6V0A4):c.2430-159C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 571,148 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (6 hom., cov: 26)
  • Exomes 𝑓: 0.012 (38 hom.)
• Consequence: ATP6V0A4 NM_020632.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.535

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-138706876-G-A is Benign according to our data. Variant chr7-138706876-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1217502.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6V0A4	NM_020632.3	c.2430-159C>T		intron_variant		ENST00000310018.7
ATP6V0A4	NM_130840.3	c.2430-159C>T		intron_variant
ATP6V0A4	NM_130841.3	c.2430-159C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6V0A4	ENST00000310018.7	c.2430-159C>T		intron_variant		1	NM_020632.3	P1

Frequencies

GnomAD3 genomes AF: 0.00636 AC: 909 AN: 143016 Hom.: 6 Cov.: 26

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.0124

Gnomad AMR AF: 0.00311

Gnomad ASJ AF: 0.00235

Gnomad EAS AF: 0.000203

Gnomad SAS AF: 0.00606

Gnomad FIN AF: 0.00770

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00207

GnomAD4 exome AF: 0.0117 AC: 5003 AN: 428072 Hom.: 38 AF XY: 0.0117 AC XY: 2341 AN XY: 200894

Gnomad4 AFR exome AF: 0.000525

Gnomad4 AMR exome AF: 0.00192

Gnomad4 ASJ exome AF: 0.00311

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00764

Gnomad4 FIN exome AF: 0.0141

Gnomad4 NFE exome AF: 0.0123

Gnomad4 OTH exome AF: 0.00800

GnomAD4 genome AF: 0.00635 AC: 909 AN: 143076 Hom.: 6 Cov.: 26 AF XY: 0.00622 AC XY: 430 AN XY: 69132

Gnomad4 AFR AF: 0.00183

Gnomad4 AMR AF: 0.00310

Gnomad4 ASJ AF: 0.00235

Gnomad4 EAS AF: 0.000204

Gnomad4 SAS AF: 0.00607

Gnomad4 FIN AF: 0.00770

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.00205

Alfa AF: 0.00805 Hom.: 3

Bravo AF: 0.00521

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 13, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.78
Dann	Benign	0.68

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: rs555283003; hg19: chr7-138391621;