Submissions for variant NM_012431.3(SEMA3E):c.479C>T (p.Ser160Leu)

gnomAD frequency: 0.00006  dbSNP: rs142392597

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001361717	SCV001557701	uncertain significance	CHARGE association	2023-09-09	criteria provided, single submitter	clinical testing	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. This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 160 of the SEMA3E protein (p.Ser160Leu). This variant is present in population databases (rs142392597, 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: 1053381). 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.
Ambry Genetics	RCV002547780	SCV003751494	uncertain significance	Inborn genetic diseases	2022-06-29	criteria provided, single submitter	clinical testing	The c.479C>T (p.S160L) alteration is located in exon 5 (coding exon 5) of the SEMA3E gene. This alteration results from a C to T substitution at nucleotide position 479, causing the serine (S) at amino acid position 160 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003399163	SCV004103708	uncertain significance	SEMA3E-related condition	2023-04-20	criteria provided, single submitter	clinical testing	The SEMA3E c.479C>T variant is predicted to result in the amino acid substitution p.Ser160Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.017% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-83047777-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529257	SCV001742405	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001529257	SCV001930675	likely benign	not provided		no assertion criteria provided	clinical testing