ClinVar Miner

Submissions for variant NM_001253852.3(AP4B1):c.505C>A (p.Arg169Ser)

dbSNP: rs753402898
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001299144 SCV001488223 uncertain significance Hereditary spastic paraplegia 47 2022-07-30 criteria provided, single submitter clinical testing 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1002684). This variant has not been reported in the literature in individuals affected with AP4B1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 169 of the AP4B1 protein (p.Arg169Ser).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002509652 SCV002819272 uncertain significance not specified 2022-12-05 criteria provided, single submitter clinical testing Variant summary: AP4B1 c.505C>A (p.Arg169Ser) results in a non-conservative amino acid change located in the Clathrin/coatomer adaptor, adaptin-like, N-terminal domain (IPR002553) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251464 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.505C>A in individuals affected with Spastic Paraplegia 47, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab RCV001299144 SCV004050686 uncertain significance Hereditary spastic paraplegia 47 2023-04-11 criteria provided, single submitter clinical testing

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