ClinVar Miner

Submissions for variant NM_020632.3(ATP6V0A4):c.812T>A (p.Ile271Asn)

gnomAD frequency: 0.00006  dbSNP: rs147475779
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000349852 SCV000466917 uncertain significance Autosomal recessive distal renal tubular acidosis 2018-01-12 criteria provided, single submitter clinical testing 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Fulgent Genetics, Fulgent Genetics RCV002481233 SCV002793101 uncertain significance Renal tubular acidosis, distal, 3, with or without sensorineural hearing loss 2022-03-31 criteria provided, single submitter clinical testing
Invitae RCV002523584 SCV003261959 uncertain significance not provided 2022-04-20 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 271 of the ATP6V0A4 protein (p.Ile271Asn). This variant is present in population databases (rs147475779, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ATP6V0A4-related conditions. ClinVar contains an entry for this variant (Variation ID: 359024). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV003168556 SCV003880590 uncertain significance Inborn genetic diseases 2023-02-27 criteria provided, single submitter clinical testing The c.812T>A (p.I271N) alteration is located in exon 10 (coding exon 8) of the ATP6V0A4 gene. This alteration results from a T to A substitution at nucleotide position 812, causing the isoleucine (I) at amino acid position 271 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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