rs58568563
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_020632.3(ATP6V0A4):c.1155C>T(p.Val385=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,613,930 control chromosomes in the GnomAD database, including 1,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.049 ( 548 hom., cov: 31)
Exomes 𝑓: 0.0087 ( 777 hom. )
Consequence
ATP6V0A4
NM_020632.3 synonymous
NM_020632.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -7.11
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 7-138749192-G-A is Benign according to our data. Variant chr7-138749192-G-A is described in ClinVar as [Benign]. Clinvar id is 359019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-7.11 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP6V0A4 | NM_020632.3 | c.1155C>T | p.Val385= | synonymous_variant | 12/22 | ENST00000310018.7 | |
ATP6V0A4 | NM_130840.3 | c.1155C>T | p.Val385= | synonymous_variant | 11/21 | ||
ATP6V0A4 | NM_130841.3 | c.1155C>T | p.Val385= | synonymous_variant | 11/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP6V0A4 | ENST00000310018.7 | c.1155C>T | p.Val385= | synonymous_variant | 12/22 | 1 | NM_020632.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0488 AC: 7418AN: 151942Hom.: 546 Cov.: 31
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GnomAD3 exomes AF: 0.0219 AC: 5510AN: 251474Hom.: 354 AF XY: 0.0181 AC XY: 2464AN XY: 135908
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GnomAD4 exome AF: 0.00872 AC: 12741AN: 1461870Hom.: 777 Cov.: 32 AF XY: 0.00811 AC XY: 5898AN XY: 727240
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GnomAD4 genome AF: 0.0489 AC: 7431AN: 152060Hom.: 548 Cov.: 31 AF XY: 0.0480 AC XY: 3568AN XY: 74340
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 21, 2016 | p.Val385Val in exon 12 of ATP6V0A4: This variant is not expected to have clinica l significance because it does not alter an amino acid residue, is not located w ithin the splice consensus sequence, and has been identified in 15.30% (1592/104 06) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs58568563). - |
Autosomal recessive distal renal tubular acidosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at