Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Equipe Genetique des Anomalies du Developpement, |
RCV000677636 | SCV000803766 | likely pathogenic | Acne inversa, familial, 1 | 2017-12-19 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003558532 | SCV004292943 | uncertain significance | not provided | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 315 of the NCSTN protein (p.Ala315Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with acne inversa (PMID: 26463457). ClinVar contains an entry for this variant (Variation ID: 559854). 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 NCSTN protein function with a negative predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |