ClinVar Miner

Submissions for variant NM_014855.3(AP5Z1):c.556T>C (p.Tyr186His)

gnomAD frequency: 0.00003  dbSNP: rs1000589136
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001755145 SCV001995999 uncertain significance not provided 2019-09-24 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV002540453 SCV003475725 uncertain significance Hereditary spastic paraplegia 48 2022-11-28 criteria provided, single submitter clinical testing This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 186 of the AP5Z1 protein (p.Tyr186His). This variant has not been reported in the literature in individuals affected with AP5Z1-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt AP5Z1 protein function. ClinVar contains an entry for this variant (Variation ID: 1312391).

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