ClinVar Miner

Submissions for variant NM_004722.4(AP4M1):c.407C>T (p.Thr136Met)

gnomAD frequency: 0.00043  dbSNP: rs138131967
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV001880056 SCV001441385 uncertain significance Hereditary spastic paraplegia 50 2020-02-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001880056 SCV002124168 uncertain significance Hereditary spastic paraplegia 50 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 136 of the AP4M1 protein (p.Thr136Met). This variant is present in population databases (rs138131967, gnomAD 0.1%). 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: 983377). 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 AP4M1 protein function with a negative predictive value of 80%. 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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