Submissions for variant NM_020778.5(ALPK3):c.1688T>C (p.Met563Thr)

dbSNP: rs150028343

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001730273	SCV002576969	uncertain significance	not provided	2022-09-28	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp	RCV001730273	SCV005702538	uncertain significance	not provided	2024-10-23	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 765 of the ALPK3 protein (p.Met765Thr). This variant is present in population databases (rs150028343, gnomAD 0.006%). 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: 1299846). 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 not expected to disrupt ALPK3 protein function with a negative 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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001730273	SCV001978366	likely benign	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001730273	SCV001978519	likely benign	not provided		no assertion criteria provided	clinical testing