ClinVar Miner

Submissions for variant NM_030962.3(SBF2):c.3127A>G (p.Ile1043Val) (rs147438385)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000517667 SCV000615008 uncertain significance not specified 2017-02-27 criteria provided, single submitter clinical testing
GeneDx RCV000767058 SCV000620694 uncertain significance not provided 2017-09-11 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SBF2 gene. The c.3127 A>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.3127 A>G variant is observed in 13/66692 (0.02%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.3127 A>G creates a cryptic acceptor site for intron 24 which may supplant the natural acceptor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. If the c.3127 A>G variant does not affect splicing, it will result in the I1043V missense change. The I1043V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000204547 SCV000261352 uncertain significance Charcot-Marie-Tooth disease type 4 2018-11-16 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 1043 of the SBF2 protein (p.Ile1043Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs147438385, ExAC 0.02%). This variant has not been reported in the literature in individuals with SBF2-related disease. ClinVar contains an entry for this variant (Variation ID: 220646). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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.