ClinVar Miner

Submissions for variant NM_001253852.3(AP4B1):c.175A>G (p.Thr59Ala)

gnomAD frequency: 0.00008  dbSNP: rs151293980
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000528134 SCV000651197 uncertain significance Hereditary spastic paraplegia 47 2025-01-13 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 59 of the AP4B1 protein (p.Thr59Ala). This variant is present in population databases (rs151293980, gnomAD 0.02%). 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: 472194). 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) indicates that this missense variant is not expected to disrupt AP4B1 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.
GeneDx RCV001799681 SCV002044087 uncertain significance not provided 2021-06-25 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25552650, 27535533)
Ambry Genetics RCV002404524 SCV002714364 uncertain significance Inborn genetic diseases 2022-12-13 criteria provided, single submitter clinical testing The c.175A>G (p.T59A) alteration is located in exon 3 (coding exon 2) of the AP4B1 gene. This alteration results from a A to G substitution at nucleotide position 175, causing the threonine (T) at amino acid position 59 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000528134 SCV004050704 uncertain significance Hereditary spastic paraplegia 47 2023-04-11 criteria provided, single submitter clinical testing

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