ClinVar Miner

Submissions for variant NM_012431.3(SEMA3E):c.1991C>T (p.Thr664Met)

gnomAD frequency: 0.00001  dbSNP: rs375536813
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000998823 SCV001155110 uncertain significance not provided 2018-05-01 criteria provided, single submitter clinical testing
Invitae RCV001053945 SCV001218232 uncertain significance CHARGE association 2023-08-04 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 664 of the SEMA3E protein (p.Thr664Met). This variant is present in population databases (rs375536813, gnomAD 0.007%). 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: 810119). 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. 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 RCV002505524 SCV002815342 uncertain significance CHARGE association; Hypogonadotropic hypogonadism 7 with or without anosmia 2021-10-30 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000998823 SCV001551413 uncertain significance not provided no assertion criteria provided clinical testing The SEMA3E p.Thr604Met variant was not identified in the literature nor was it identified in the ClinVar, Cosmic or MutDB databases. The variant was identified in dbSNP (ID: rs375536813) and LOVD 3.0. The variant was identified in control databases in 1 of 249208 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following population: European (non-Finnish) in 1 of 112562 chromosomes (freq: 0.000009), while the variant was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, and South Asian populations. The p.Thr604 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, BLOSUM, and MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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