ClinVar Miner

Submissions for variant NM_020778.5(ALPK3):c.3113G>A (p.Arg1038His)

gnomAD frequency: 0.00006  dbSNP: rs146371614
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001583246 SCV001810896 uncertain significance not provided 2021-01-21 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001583246 SCV002224292 uncertain significance not provided 2024-10-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1240 of the ALPK3 protein (p.Arg1240His). This variant is present in population databases (rs146371614, gnomAD 0.05%). 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: 1211437). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ALPK3 protein function with a positive predictive value of 80%. 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 RCV002343754 SCV002620247 uncertain significance Cardiovascular phenotype 2023-01-06 criteria provided, single submitter clinical testing The p.R1240H variant (also known as c.3719G>A), located in coding exon 6 of the ALPK3 gene, results from a G to A substitution at nucleotide position 3719. The arginine at codon 1240 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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