ClinVar

Description

p.Ala30Val (GCT>GTT): c.89 C>T in exon 1 of the PNPO gene (NM_018129.3). The Ala30Val missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Ala30Val alters a position that is well conserved through mammals in the PNPO protein and another missense mutation at a nearby codon (Asp33Val) has been reported in association with PNPO deficiency (Schmitt et al., 2010; Goyal et al., 2013). However, the Ala30Val amino substitution is conservative as both Alanine and Valine are uncharged, non-polar amino acid residues. In addition, in silico analysis predicts this variant likely has a benign effect on the protein structure/function. Therefore, based on the currently available information, it is unclear whether Ala30Val is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).