ClinVar Miner

Submissions for variant NM_002637.4(PHKA1):c.3443T>G (p.Ile1148Ser)

gnomAD frequency: 0.00015  dbSNP: rs782365144
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497509 SCV000590078 uncertain significance not provided 2018-08-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the PHKA1 gene. The I1148S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The I1148S variant is observed in 2/8502 (0.02%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I1148S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in Human Gene Mutation Database in association with PHKA1-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000702439 SCV000831294 uncertain significance Glycogen storage disease IXd 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1148 of the PHKA1 protein (p.Ile1148Ser). This variant is present in population databases (rs782365144, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of PHKA1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 432361). 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 tolerated. 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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