ClinVar Miner

Submissions for variant NM_053013.4(ENO3):c.467G>A (p.Gly156Asp)

gnomAD frequency: 0.00019  dbSNP: rs121918403
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000018092 SCV001517206 uncertain significance Glycogen storage disease due to muscle beta-enolase deficiency 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 156 of the ENO3 protein (p.Gly156Asp). This variant is present in population databases (rs121918403, gnomAD 0.03%). This missense change has been observed in individual(s) with glycogen storage disease type XIII (PMID: 11506403). ClinVar contains an entry for this variant (Variation ID: 16617). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ENO3 protein function. Experimental studies have shown that this missense change affects ENO3 function (PMID: 18070103). 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.
GeneDx RCV001582485 SCV001812489 uncertain significance not provided 2020-09-30 criteria provided, single submitter clinical testing Published protein folding and stability studies of the corresponding missense variant in yeast suggests this variant reduces the stability of yeast enolase (Zhao et al., 2018); however, the clinical significance of this finding in humans remains to be determined.; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31589614, 18070103, 11506403)
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000018092 SCV002769385 likely pathogenic Glycogen storage disease due to muscle beta-enolase deficiency 2020-10-19 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Likely Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with beta-enolase deficiency. (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to aspartic acid. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (55 heterozygotes, 0 homozygotes). (SP) 0309 - Alternative amino acid changes at the same position have been observed in gnomAD (v2) (3 heterozygotes, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated C-terminal TIM barrel domain (PDB). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0803 - This variant has limited previous evidence of pathogenicity in an individual. The variant has previously been reported in a compound heterozygous patient with beta-enolase deficiency (ClinVar, OMIM, PMID: 11506403). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Functional studies in a yeast model demonstrated that the variant results in a loss of function (PMID: 18070103). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
OMIM RCV000018092 SCV000038371 pathogenic Glycogen storage disease due to muscle beta-enolase deficiency 2001-08-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.