ClinVar Miner

Submissions for variant NM_000038.6(APC):c.3847G>A (p.Ala1283Thr)

gnomAD frequency: 0.00001  dbSNP: rs1428789824
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV004563404 SCV000768132 uncertain significance Familial adenomatous polyposis 1 2022-03-05 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1283 of the APC protein (p.Ala1283Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 537474). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV003338714 SCV004059088 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-23 criteria provided, single submitter clinical testing The p.A1283T variant (also known as c.3847G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 3847. The alanine at codon 1283 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV003338714 SCV004362848 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-02 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 1283 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The 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.

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