Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV004771627 | SCV005382250 | uncertain significance | Hereditary spastic paraplegia 15 | 2023-05-20 | criteria provided, single submitter | clinical testing | The missense variant c.5303C>G(p.Ser1768Cys) in ZFYVE26 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The observed variant has allele frequency of 0.0004% in gnomAD exomes database. This variant has not been submitted to the ClinVar database. Multiple lines of computational evidence (Polyphen - possibly damaging, SIFT - tolerated and MutationTaster - polymorphism) predicts conflicting evidence on protein structure and function for this variant. The reference amino acid change p.Ser1768Cys in ZFYVE26 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Ser at position 1768 is changed to a Cys changing protein sequence and it might alter its composition and physicochemical properties. For these reasons, this variant has been classified as Uncertain Significance (VUS). In the absence of another reportable variant in ZFYVE26 gene, the molecular diagnosis is not confirmed. |