ClinVar Miner

Submissions for variant NM_152703.5(SAMD9L):c.3893G>A (p.Arg1298His)

gnomAD frequency: 0.00002  dbSNP: rs1010548594
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001903893 SCV002174941 uncertain significance not provided 2024-06-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1298 of the SAMD9L protein (p.Arg1298His). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 1405557). 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 SAMD9L 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.
Johns Hopkins Genomics, Johns Hopkins University RCV002282643 SCV002570255 uncertain significance Ataxia-pancytopenia syndrome 2022-05-07 criteria provided, single submitter clinical testing This SAMD9L variant (rs1010548594) is rare (<0.1%) in a large population dataset (gnomAD: 2/249554 total alleles; 0.0008%; no homozygotes) and has been reported in ClinVar. This missense variant has not been reported in individuals with SCA49 in the literature. Three bioinformatic tools queried predict that this substitution would be tolerated; the arginine residue at this position is conserved across most primates, but weakly conserved across other vertebrate species assessed. Bioinformatic analysis predicts that this variant would not affect normal exon 5 splicing, although this has not been confirmed experimentally to our knowledge. Due to insufficient evidence, we consider the clinical significance of c.3893G>A to be uncertain at this time.
GeneDx RCV001903893 SCV005372045 uncertain significance not provided 2023-07-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 35310830)
Ambry Genetics RCV004955793 SCV005499214 uncertain significance Inborn genetic diseases 2024-12-04 criteria provided, single submitter clinical testing The c.3893G>A (p.R1298H) alteration is located in exon 5 (coding exon 1) of the SAMD9L gene. This alteration results from a G to A substitution at nucleotide position 3893, causing the arginine (R) at amino acid position 1298 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.