Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000658182 | SCV000779953 | uncertain significance | not provided | 2018-05-15 | criteria provided, single submitter | clinical testing | The N616T variant in the POLR3A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N616T variant is observed in 3/33578 (0.009%) alleles from individuals of Latino background in large population cohorts (Lek et al., 2016). The N616T variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret N616T as a variant of uncertain significance. |
Labcorp Genetics |
RCV000658182 | SCV002947493 | uncertain significance | not provided | 2023-11-22 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 616 of the POLR3A protein (p.Asn616Thr). This variant is present in population databases (rs779523101, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with POLR3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 546325). 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 POLR3A 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. |
Ambry Genetics | RCV004957976 | SCV005481797 | uncertain significance | Inborn genetic diseases | 2024-12-04 | criteria provided, single submitter | clinical testing | The c.1847A>C (p.N616T) alteration is located in exon 14 (coding exon 14) of the POLR3A gene. This alteration results from a A to C substitution at nucleotide position 1847, causing the asparagine (N) at amino acid position 616 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |