ClinVar Miner

Submissions for variant NM_002778.4(PSAP):c.1075G>A (p.Glu359Lys)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV005087082 SCV005719483 uncertain significance Sphingolipid activator protein 1 deficiency 2024-03-25 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 359 of the PSAP protein (p.Glu359Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PSAP-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PSAP protein function with a negative predictive value of 80%. This variant disrupts the p.Glu359 amino acid residue in PSAP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 35456468). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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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