ClinVar Miner

Submissions for variant NM_012431.3(SEMA3E):c.1498C>T (p.Arg500Trp)

dbSNP: rs111300014
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000697569 SCV000826188 uncertain significance CHARGE syndrome 2022-12-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 500 of the SEMA3E protein (p.Arg500Trp). This variant is present in population databases (rs111300014, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SEMA3E-related conditions. ClinVar contains an entry for this variant (Variation ID: 575377). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
GeneDx RCV001813799 SCV002061012 uncertain significance not provided 2022-01-11 criteria provided, single submitter clinical testing Observed in a proband with Kallman syndrome, congenital hypogonadotrophic hypogonadism, cryptorchidism, azoospermia, olfactory nerve center maldevelopment, and vitiligo, but familial segregation information was not included (Zhang et al., 2021); Observed in a proband with pituitary stalk interruption syndrome with decreased growth rate, deficiency of thyrotropin, Fanconi syndrome, microphthalmia, and cryptorchidism, but familial segregation information was not included and the proband was reported to have potentially causative variants in other genes (Brauner et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34348883, 33270637)
Fulgent Genetics, Fulgent Genetics RCV002485702 SCV002778465 uncertain significance CHARGE syndrome; Hypogonadotropic hypogonadism 7 with or without anosmia 2022-05-11 criteria provided, single submitter clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund RCV001813799 SCV005198207 uncertain significance not provided 2022-06-30 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004745555 SCV005359047 uncertain significance SEMA3E-related disorder 2024-04-17 no assertion criteria provided clinical testing The SEMA3E c.1498C>T variant is predicted to result in the amino acid substitution p.Arg500Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.022% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.