Submissions for variant NM_006947.4(SRP72):c.1294G>A (p.Ala432Thr)

gnomAD frequency: 0.00019  dbSNP: rs201102960

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV001820459	SCV002067795	uncertain significance	not specified	2019-11-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002542626	SCV003030403	uncertain significance	not provided	2025-01-27	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 432 of the SRP72 protein (p.Ala432Thr). This variant is present in population databases (rs201102960, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SRP72-related conditions. ClinVar contains an entry for this variant (Variation ID: 1337445). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SRP72 protein function with a negative predictive value of 80%. 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	RCV001820459	SCV005172608	uncertain significance	not specified	2024-11-20	criteria provided, single submitter	clinical testing	The p.A432T variant (also known as c.1294G>A), located in coding exon 13 of the SRP72 gene, results from a G to A substitution at nucleotide position 1294. The alanine at codon 432 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
GeneDx	RCV002542626	SCV005421545	uncertain significance	not provided	2024-06-05	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV003913408	SCV004733039	likely benign	SRP72-related disorder	2022-03-30	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).