ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.98C>T (p.Ser33Leu)

gnomAD frequency: 0.00004  dbSNP: rs139282091
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000531703 SCV000623360 uncertain significance Bloom syndrome 2024-11-24 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 33 of the BLM protein (p.Ser33Leu). This variant is present in population databases (rs139282091, gnomAD 0.005%). 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: 133703). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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 RCV000568835 SCV000672942 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-02 criteria provided, single submitter clinical testing The p.S33L variant (also known as c.98C>T), located in coding exon 1 of the BLM gene, results from a C to T substitution at nucleotide position 98. The amino acid change results in serine to leucine at codon 33, an amino acid with dissimilar properties. This amino acid position is not 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003237720 SCV002010744 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003237720 SCV004222514 uncertain significance not provided 2023-08-16 criteria provided, single submitter clinical testing In the published literature, this variant has been reported in unaffected individuals (PMID: 24728327 (20104)). The frequency of this variant in the general population, 0.000027 (7/262566 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.
ITMI RCV000120232 SCV000084379 not provided not specified 2013-09-19 no assertion provided reference population
Natera, Inc. RCV000531703 SCV002089883 uncertain significance Bloom syndrome 2018-11-17 no assertion criteria provided clinical testing

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