ClinVar Miner

Submissions for variant NM_006393.3(NEBL):c.56G>A (p.Gly19Glu)

gnomAD frequency: 0.00006  dbSNP: rs727503338
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000151550 SCV000199685 likely benign not specified 2014-04-04 criteria provided, single submitter clinical testing Gly19Glu in exon 1 of NEBL: This variant is not expected to have clinical signif icance due to a lack of conservation across species, including mammals. Of note, >20 mammals and other species have a glutamine (Glu) at this position despite h igh nearby amino acid conservation. In addition, computational prediction tools do not suggest a high likelihood of impact to the protein.
Invitae RCV002514917 SCV003250380 uncertain significance Primary dilated cardiomyopathy 2023-11-28 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 19 of the NEBL protein (p.Gly19Glu). This variant is present in population databases (rs727503338, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with NEBL-related conditions. ClinVar contains an entry for this variant (Variation ID: 164772). 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 glutamic acid 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 RCV000151550 SCV004085420 likely benign not specified 2023-07-25 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.

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