Submissions for variant NM_012431.3(SEMA3E):c.1290A>T (p.Lys430Asn)

gnomAD frequency: 0.00008  dbSNP: rs61729605

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001054873	SCV001219231	uncertain significance	CHARGE syndrome	2024-11-05	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 430 of the SEMA3E protein (p.Lys430Asn). This variant is present in population databases (rs61729605, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. 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: 850659). 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.
Fulgent Genetics, Fulgent Genetics	RCV002497423	SCV002806764	uncertain significance	CHARGE syndrome; Hypogonadotropic hypogonadism 7 with or without anosmia	2021-12-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003963016	SCV004783603	likely benign	SEMA3E-related disorder	2022-10-20	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).