ClinVar Miner

Submissions for variant NM_020778.5(ALPK3):c.221A>C (p.Glu74Ala)

gnomAD frequency: 0.00010  dbSNP: rs533505673
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001562554 SCV001785337 uncertain significance not provided 2020-10-19 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002424984 SCV002680160 uncertain significance Cardiovascular phenotype 2023-09-12 criteria provided, single submitter clinical testing The p.E276A variant (also known as c.827A>C), located in coding exon 3 of the ALPK3 gene, results from an A to C substitution at nucleotide position 827. The glutamic acid at codon 276 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001562554 SCV003463047 uncertain significance not provided 2025-01-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 276 of the ALPK3 protein (p.Glu276Ala). This variant is present in population databases (rs533505673, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ALPK3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1198412). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.

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