ClinVar Miner

Submissions for variant NM_004722.4(AP4M1):c.643C>T (p.Arg215Trp)

gnomAD frequency: 0.00001  dbSNP: rs146445385
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001848219 SCV002105817 uncertain significance Hereditary spastic paraplegia 2018-03-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002543377 SCV003521760 uncertain significance Hereditary spastic paraplegia 50 2024-10-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 215 of the AP4M1 protein (p.Arg215Trp). This variant is present in population databases (rs146445385, gnomAD 0.04%). 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: 1344116). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AP4M1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

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