Submissions for variant NM_001160372.4(TRAPPC9):c.3175G>A (p.Ala1059Thr)

gnomAD frequency: 0.00056  dbSNP: rs150200902

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000194313	SCV000249193	uncertain significance	not specified	2015-02-26	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000390442	SCV000472168	uncertain significance	Intellectual Disability, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000766965	SCV000514964	likely benign	not provided	2019-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002311307	SCV000846226	likely benign	Inborn genetic diseases	2021-04-08	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics	RCV000764741	SCV000895878	uncertain significance	Intellectual disability, autosomal recessive 13	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000766965	SCV002136766	uncertain significance	not provided	2024-01-22	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1157 of the TRAPPC9 protein (p.Ala1157Thr). This variant is present in population databases (rs150200902, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with TRAPPC9-related conditions. ClinVar contains an entry for this variant (Variation ID: 212432). 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.
PreventionGenetics, part of Exact Sciences	RCV004745263	SCV005351374	uncertain significance	TRAPPC9-related disorder	2024-07-05	no assertion criteria provided	clinical testing	The TRAPPC9 c.3469G>A variant is predicted to result in the amino acid substitution p.Ala1157Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.15% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.