ClinVar Miner

Submissions for variant NM_015047.3(EMC1):c.2455G>A (p.Ala819Thr)

gnomAD frequency: 0.00016  dbSNP: rs371524055
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001339271 SCV001533003 uncertain significance not provided 2024-12-19 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 819 of the EMC1 protein (p.Ala819Thr). This variant is present in population databases (rs371524055, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with EMC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1036283). 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 EMC1 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.
New York Genome Center RCV003448395 SCV004176222 uncertain significance Cerebellar atrophy, visual impairment, and psychomotor retardation; 2023-05-11 criteria provided, single submitter clinical testing The c.2455G>A variant in EMC1 has not previously been reported in the literature and it has been deposited in ClinVar [ClinVar ID: 1036283] as a Variant of Uncertain Significance. The c.2455G>A variant is observed in 71 alleles (0.012% minor allele frequency with 0 homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2,TOPMed Freeze 8). The c.2455G>A variant is located in exon 20 of this 23-exon gene and is predicted to replace a conserved alanine amino acid with threonine at position 819 (p.(Ala819Thr)) in the DUF1620 domain of the protein [PMID: 26942288, 35234901]. In silico predictions for p.(Ala819Thr) are inconclusive of the variant's effect [(CADD v1.6 = 22.7, REVEL = 0.067)]; however, there are no functional studies to support or refute these predictions. Based on available evidence this inherited c.2455G>A p.( Ala819Thr) variant identified in EMC1 is classified as a Variant of Uncertain Significance.
GeneDx RCV001339271 SCV005383035 uncertain significance not provided 2024-01-17 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

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