ClinVar Miner

Submissions for variant NM_012431.3(SEMA3E):c.781G>A (p.Ala261Thr)

dbSNP: rs773917768
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002029445 SCV002305559 uncertain significance CHARGE syndrome 2024-03-26 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 261 of the SEMA3E protein (p.Ala261Thr). This variant is present in population databases (rs773917768, gnomAD 0.006%). 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: 1514639). 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 SEMA3E 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.
Fulgent Genetics, Fulgent Genetics RCV002486717 SCV002777229 uncertain significance CHARGE syndrome; Hypogonadotropic hypogonadism 7 with or without anosmia 2022-04-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV004046816 SCV004946946 likely benign not specified 2024-01-09 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences RCV004746585 SCV005344602 uncertain significance SEMA3E-related disorder 2024-05-15 no assertion criteria provided clinical testing The SEMA3E c.781G>A variant is predicted to result in the amino acid substitution p.Ala261Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0054% 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.

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