Submissions for variant NM_012210.4(TRIM32):c.1012G>A (p.Ala338Thr)

gnomAD frequency: 0.00008  dbSNP: rs141806013

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000521332	SCV000620983	uncertain significance	not provided	2017-09-18	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the TRIM32 gene. The A338T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A338T variant is observed in 10/66460 (0.02%) alleles from individuals of European background in the ExAC dataset (Lek et al., 2016). The A338T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000549384	SCV000636496	uncertain significance	Bardet-Biedl syndrome	2022-10-13	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 338 of the TRIM32 protein (p.Ala338Thr). This variant is present in population databases (rs141806013, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TRIM32-related conditions. ClinVar contains an entry for this variant (Variation ID: 452197). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Athena Diagnostics	RCV000521332	SCV001475697	uncertain significance	not provided	2019-12-30	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002481727	SCV002781695	uncertain significance	Sarcotubular myopathy; Bardet-Biedl syndrome 11	2022-02-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002525230	SCV003683387	uncertain significance	Inborn genetic diseases	2022-09-06	criteria provided, single submitter	clinical testing	The c.1012G>A (p.A338T) alteration is located in exon 2 (coding exon 1) of the TRIM32 gene. This alteration results from a G to A substitution at nucleotide position 1012, causing the alanine (A) at amino acid position 338 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000521332	SCV003823470	uncertain significance	not provided	2021-04-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003962451	SCV004776745	uncertain significance	TRIM32-related disorder	2024-08-12	no assertion criteria provided	clinical testing	The TRIM32 c.1012G>A variant is predicted to result in the amino acid substitution p.Ala338Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.015% of alleles in individuals of European (non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.