rs3807154
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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):āc.1812T>Cā(p.His604=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 1,613,270 control chromosomes in the GnomAD database, including 410,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.66 ( 34209 hom., cov: 30)
Exomes š: 0.72 ( 376173 hom. )
Consequence
ATP6V0A4
NM_020632.3 synonymous
NM_020632.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0700
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=-0.9).
BP6
?
Variant 7-138732973-A-G is Benign according to our data. Variant chr7-138732973-A-G is described in ClinVar as [Benign]. Clinvar id is 261343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-138732973-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.07 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP6V0A4 | NM_020632.3 | c.1812T>C | p.His604= | synonymous_variant | 17/22 | ENST00000310018.7 | |
ATP6V0A4 | NM_130840.3 | c.1812T>C | p.His604= | synonymous_variant | 16/21 | ||
ATP6V0A4 | NM_130841.3 | c.1812T>C | p.His604= | synonymous_variant | 16/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP6V0A4 | ENST00000310018.7 | c.1812T>C | p.His604= | synonymous_variant | 17/22 | 1 | NM_020632.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.660 AC: 100206AN: 151724Hom.: 34202 Cov.: 30
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GnomAD3 exomes AF: 0.729 AC: 183187AN: 251388Hom.: 67755 AF XY: 0.730 AC XY: 99185AN XY: 135854
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GnomAD4 exome AF: 0.715 AC: 1045437AN: 1461428Hom.: 376173 Cov.: 60 AF XY: 0.717 AC XY: 521051AN XY: 727064
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GnomAD4 genome ? AF: 0.660 AC: 100240AN: 151842Hom.: 34209 Cov.: 30 AF XY: 0.665 AC XY: 49374AN XY: 74212
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | - - |
Autosomal recessive distal renal tubular acidosis Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at