ClinVar Miner

Submissions for variant NM_004722.4(AP4M1):c.1225T>C (p.Phe409Leu)

dbSNP: rs760907496
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences 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

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