Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Research Center, |
RCV000625788 | SCV000746338 | likely pathogenic | Hereditary spastic paraplegia 50 | 2020-05-03 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000625788 | SCV002125117 | uncertain significance | Hereditary spastic paraplegia 50 | 2022-08-09 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 409 of the AP4M1 protein (p.Phe409Leu). This variant is present in population databases (rs760907496, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with AP4M1-related conditions. ClinVar contains an entry for this variant (Variation ID: 522649). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
DASA | RCV000625788 | SCV002318952 | likely pathogenic | Hereditary spastic paraplegia 50 | 2022-03-25 | criteria provided, single submitter | clinical testing | The variant is located in a mutational hot spot and/or critical and well-established functional domain (Adap_comp_sub) - PM1. This variant is not present in population databases (rs760907496- gnomAD; ABraOM no frequency - http://abraom.ib.usp.br.) - PM2. The p.(Phe409Leu) was detected in a homozygous state in the analyzed sample - - PM3_supporting. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is likely pathogenic |