ClinVar Miner

Submissions for variant NM_001253852.3(AP4B1):c.1643C>T (p.Pro548Leu)

gnomAD frequency: 0.00003  dbSNP: rs149723440
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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 RCV000467596 SCV000548561 uncertain significance Hereditary spastic paraplegia 47 2022-05-21 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 548 of the AP4B1 protein (p.Pro548Leu). This variant is present in population databases (rs149723440, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with AP4B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 408759). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Ambry Genetics RCV002402262 SCV002704598 uncertain significance Inborn genetic diseases 2018-05-21 criteria provided, single submitter clinical testing The p.P548L variant (also known as c.1643C>T), located in coding exon 9 of the AP4B1 gene, results from a C to T substitution at nucleotide position 1643. The proline at codon 548 is replaced by leucine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000467596 SCV004050641 uncertain significance Hereditary spastic paraplegia 47 2023-04-11 criteria provided, single submitter clinical testing

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