Submissions for variant NM_015650.4(TRAF3IP1):c.115A>G (p.Ile39Val)

gnomAD frequency: 0.00044  dbSNP: rs370097041

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001064316	SCV001229209	uncertain significance	not provided	2022-10-05	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 39 of the TRAF3IP1 protein (p.Ile39Val). This variant is present in population databases (rs370097041, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with TRAF3IP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 858440). 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 TRAF3IP1 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.
Ambry Genetics	RCV002554463	SCV003531874	uncertain significance	Inborn genetic diseases	2021-12-07	criteria provided, single submitter	clinical testing	The c.115A>G (p.I39V) alteration is located in exon 1 (coding exon 1) of the TRAF3IP1 gene. This alteration results from a A to G substitution at nucleotide position 115, causing the isoleucine (I) at amino acid position 39 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV001064316	SCV005333520	uncertain significance	not provided	2023-09-21	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV003963026	SCV004784839	likely benign	TRAF3IP1-related disorder	2023-07-29	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).