Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002007678 | SCV002260320 | uncertain significance | not provided | 2024-06-12 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 161 of the SAMD9L protein (p.Leu161Phe). This variant is present in population databases (rs375402434, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SAMD9L-related conditions. ClinVar contains an entry for this variant (Variation ID: 1474656). 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. 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. |
| St. |
RCV002254741 | SCV002525982 | uncertain significance | Ataxia-pancytopenia syndrome | 2022-02-24 | criteria provided, single submitter | clinical testing | The SAMD9L c.483G>T (p.Leu161Phe) missense change has a maximum subpopulation frequency of 0.0017% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/7-92764802-C-A?dataset=gnomad_r2_1). Seven of seven in silico tools predict a benign effect of this variant on protein function, but to our knowledge these predictions have not been confirmed by functional assays. However, In silico predictions have not been found to correlate with syndromic risk and are thus not considered supporting evidence of a pathogenic or benign effect (PMID: 34621053). To our knowledge, this variant has not been reported in individuals with ataxia-pancytopenia syndrome. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: No criteria met |
| Ambry Genetics | RCV004956040 | SCV005497733 | uncertain significance | Inborn genetic diseases | 2024-11-24 | criteria provided, single submitter | clinical testing | The p.L161F variant (also known as c.483G>T), located in coding exon 1 of the SAMD9L gene, results from a G to T substitution at nucleotide position 483. The leucine at codon 161 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Prevention |
RCV004738480 | SCV005352689 | uncertain significance | SAMD9L-related disorder | 2024-08-16 | no assertion criteria provided | clinical testing | The SAMD9L c.483G>T variant is predicted to result in the amino acid substitution p.Leu161Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/1474656/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |