ClinVar Miner

Submissions for variant NM_012431.3(SEMA3E):c.2133G>T (p.Lys711Asn)

gnomAD frequency: 0.00008  dbSNP: rs768818178
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000800132 SCV000939832 uncertain significance CHARGE association 2023-12-12 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 711 of the SEMA3E protein (p.Lys711Asn). This variant is present in population databases (rs768818178, gnomAD 0.009%). 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: 645948). 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 disruptive. 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 RCV001548099 SCV001767953 uncertain significance not provided 2023-06-05 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; K711N has not been published as a pathogenic variant, nor has it been reported as a benign variant in association with a hearing loss phenotype; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (Richards et al., 2015); This variant is associated with the following publications: (PMID: 30661757)
Fulgent Genetics, Fulgent Genetics RCV002487688 SCV002777619 uncertain significance CHARGE association; Hypogonadotropic hypogonadism 7 with or without anosmia 2021-09-19 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003424347 SCV004118066 uncertain significance SEMA3E-related condition 2023-10-27 criteria provided, single submitter clinical testing The SEMA3E c.2133G>T variant is predicted to result in the amino acid substitution p.Lys711Asn. This p.Lys411Asn substitution has been reported in one child with severe obesity. In vitro functional characterization suggests that it leads to increase protein secretion (Table 1, Table S3 in van der Klaauw et al. 2019. PubMed: 30661757). This variant is reported in 0.0093% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-82997097-C-A). 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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