Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002273019 | SCV002557571 | likely pathogenic | 46,XY sex reversal 3 | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with adrenocortical insufficiency (MIM#612964), 46,XX sex reversal 4 (MIM# 617480), premature ovarian failure 7 (MIM#612964), spermatogenic failure 8 (MIM#613957) and 46,XY sex reversal 3 (MIM#612965). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Intra-familial variability has been reported for variants in this gene (PMID: 31513305). (I) 0200 - Variant is predicted to result in a missense amino acid change from leucine to proline. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools and highly conserved with a moderate amino acid change. (SP) 0600 - Variant is located in the annotated ligand-binding domain (UniProt). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant has been reported in one 46,XY DSD individual (PMID: 28033660). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Mutant constructs transfected into human embryonic kidney TSA-201 cells demonstrated significantly reduced transactivation activity compared to WT constructs (PMID: 28033660). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |