ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.3728A>G (p.Asn1243Ser)

gnomAD frequency: 0.00001  dbSNP: rs730881363
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000537394 SCV000622446 uncertain significance Ataxia-telangiectasia syndrome 2024-07-30 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1243 of the ATM protein (p.Asn1243Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 453486). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The serine 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 RCV000567351 SCV000667835 likely benign Hereditary cancer-predisposing syndrome 2024-07-23 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health RCV000567351 SCV000912994 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-12 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 1243 of the ATM protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/243626 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Natera, Inc. RCV000537394 SCV001458189 uncertain significance Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing

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