ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1495T>A (p.Ser499Thr)

gnomAD frequency: 0.00007  dbSNP: rs371965329
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000526747 SCV000623242 uncertain significance Bloom syndrome 2025-01-06 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 499 of the BLM protein (p.Ser499Thr). This variant is present in population databases (rs371965329, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 454081). 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 BLM 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 RCV002395273 SCV002700498 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-09 criteria provided, single submitter clinical testing The p.S499T variant (also known as c.1495T>A), located in coding exon 6 of the BLM gene, results from a T to A substitution at nucleotide position 1495. The serine at codon 499 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV005000109 SCV005624236 uncertain significance not provided 2024-11-18 criteria provided, single submitter clinical testing The BLM c.1495T>A (p.Ser499Thr) variant has not been reported in individuals with BLM-related conditions in the published literature. The frequency of this variant in the general population, 0.0002 (5/24714 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc. RCV000526747 SCV001460784 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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