rs10258719

Variant names:

• chr7-138771243-A-C
• rs10258719
• NM_020632.3:c.5T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-138771243-A-C
• chr7-138771243-A-G
• chr7-138771243-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM2 PM5 BP4_Strong

The NM_020632.3(ATP6V0A4):​c.5T>G​(p.Val2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATP6V0A4 NM_020632.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr7-138771243-A-G is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.03315699).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V0A4	NM_020632.3	c.5T>G	p.Val2Gly	missense_variant	Exon 3 of 22	ENST00000310018.7	NP_065683.2
ATP6V0A4	NM_130840.3	c.5T>G	p.Val2Gly	missense_variant	Exon 2 of 21		NP_570855.2
ATP6V0A4	NM_130841.3	c.5T>G	p.Val2Gly	missense_variant	Exon 2 of 21		NP_570856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V0A4	ENST00000310018.7	c.5T>G	p.Val2Gly	missense_variant	Exon 3 of 22	1	NM_020632.3	ENSP00000308122.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1460848 Hom.: 0 Cov.: 47 AF XY: 0.00 AC XY: 0 AN XY: 726818

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.16
DEOGEN2	Benign	0.057	T;T;T;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.12	.;T;.;.;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.033	T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	-1.6	N;N;N;N;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	5.5	N;N;.;N;.
REVEL	Benign	0.18
Sift	Benign	1.0	T;T;.;T;.
Sift4G	Benign	1.0	T;T;.;T;.
Polyphen		0.014	B;B;B;B;.
Vest4		0.052
MutPred		0.45		Loss of stability (P = 0.0038);Loss of stability (P = 0.0038);Loss of stability (P = 0.0038);Loss of stability (P = 0.0038);Loss of stability (P = 0.0038);
MVP		0.58
MPC		0.25
ClinPred		0.048	T
GERP RS		1.9
Varity_R		0.044
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10258719; hg19: chr7-138455988;