ClinVar Miner

Submissions for variant NM_003079.5(SMARCE1):c.823G>A (p.Gly275Ser)

gnomAD frequency: 0.00004  dbSNP: rs745448272
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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 RCV000638923 SCV000760478 uncertain significance Familial meningioma 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 275 of the SMARCE1 protein (p.Gly275Ser). This variant is present in population databases (rs745448272, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SMARCE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 532246). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV001027312 SCV001189851 likely benign Hereditary cancer-predisposing syndrome 2021-06-29 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences RCV003392480 SCV004120710 uncertain significance SMARCE1-related disorder 2023-10-04 criteria provided, single submitter clinical testing The SMARCE1 c.823G>A variant is predicted to result in the amino acid substitution p.Gly275Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0098% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-38787170-C-T), and it has conflicting classifications in ClinVar including uncertain significance and likely benign (https://www.ncbi.nlm.nih.gov/clinvar/variation/532246/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV000638923 SCV004205030 uncertain significance Familial meningioma 2023-09-28 criteria provided, single submitter clinical testing

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