Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002582043 | SCV003491962 | uncertain significance | not provided | 2023-07-07 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 417 of the SIN3A protein (p.Pro417Leu). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 2175766). This variant has not been reported in the literature in individuals affected with SIN3A-related conditions. This variant is present in population databases (rs376704049, gnomAD 0.02%). |
| Revvity Omics, |
RCV003138523 | SCV003823271 | uncertain significance | SIN3A-related intellectual disability syndrome due to a point mutation | 2019-07-24 | criteria provided, single submitter | clinical testing | |
| Pittsburgh Clinical Genomics Laboratory, |
RCV003138523 | SCV005397837 | uncertain significance | SIN3A-related intellectual disability syndrome due to a point mutation | 2024-03-25 | criteria provided, single submitter | clinical testing | This sequence variant is a single nucleotide substitution (C>T) at position 1250 of the coding sequence of the SIN3A gene that results in a proline to leucine amino acid change at residue 417 of the SIN3 transcription regulator family member A protein. This is a previously reported variant (ClinVar 2175766) that has not been observed in an individual with a SIN3A-related disorder in the published literature, to our knowledge. This variant is present in 52 of 1613796 alleles (0.0032%) in the gnomAD v4.0.0 population dataset. Multiple bioinformatic tools predict that this amino acid change would be neutral, and the Pro417 residue at this position is well conserved across the vertebrate species examined. Studies examining the functional consequence of this variant have not been published, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this a variant of uncertain significance. ACMG Criteria: BP4, PM2 |