ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3416G>A (p.Arg1139Gln)

gnomAD frequency: 0.00001  dbSNP: rs771776126
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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 RCV000628686 SCV000749592 uncertain significance Bloom syndrome 2024-10-31 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1139 of the BLM protein (p.Arg1139Gln). This variant is present in population databases (rs771776126, gnomAD 0.01%). 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: 524818). 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 expected to disrupt BLM protein function with a positive 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.
Fulgent Genetics, Fulgent Genetics RCV000628686 SCV000896487 uncertain significance Bloom syndrome 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001020246 SCV001181699 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-29 criteria provided, single submitter clinical testing The p.R1139Q variant (also known as c.3416G>A), located in coding exon 17 of the BLM gene, results from a G to A substitution at nucleotide position 3416. The arginine at codon 1139 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Sema4, Sema4 RCV001020246 SCV002532411 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-22 criteria provided, single submitter curation
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000628686 SCV003843072 uncertain significance Bloom syndrome 2023-02-28 criteria provided, single submitter clinical testing The BLM c.3416G>A (p.Arg1139Gln) missense change has a maximum subpopulation frequency of 0.016% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Bloom syndrome. ?In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.?
Natera, Inc. RCV000628686 SCV002090563 uncertain significance Bloom syndrome 2020-01-29 no assertion criteria provided clinical testing

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