ClinVar Miner

Submissions for variant NM_000481.4(AMT):c.401A>G (p.Asn134Ser)

gnomAD frequency: 0.00006  dbSNP: rs776832405
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000428028 SCV000530865 uncertain significance not provided 2016-08-18 criteria provided, single submitter clinical testing The N134S variant in the AMT gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N134S variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N134S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret N134S as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000795074 SCV000934515 uncertain significance Glycine encephalopathy 2024-11-05 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 134 of the AMT protein (p.Asn134Ser). This variant is present in population databases (rs776832405, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with AMT-related conditions. ClinVar contains an entry for this variant (Variation ID: 388539). 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 AMT protein function with a negative predictive value of 95%. 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.
Natera, Inc. RCV000795074 SCV002081718 uncertain significance Glycine encephalopathy 2019-10-28 no assertion criteria provided clinical testing

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