ClinVar Miner

Submissions for variant NM_001243279.3(ACSF3):c.1470G>C (p.Glu490Asp) (rs147538370)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000444454 SCV000511955 uncertain significance not provided 2017-01-26 criteria provided, single submitter clinical testing An E490D missense change likely associated with combined malonic and methylmalonic aciduria (CMAMMA) was identified in the ACSF3 gene. It has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. It has been seen previously in a patient at GeneDx who also harbored a previously reported pathogenic variant in the ACSF3 gene. Furthermore, this substitution occurs at a position that is conserved across species and multiple in-silico analysis models predict that E490D is damaging to the ACSF3 protein. Therefore, E490D is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000444454 SCV001249837 likely pathogenic not provided 2021-06-01 criteria provided, single submitter clinical testing
Invitae RCV001245382 SCV001418665 pathogenic Combined malonic and methylmalonic aciduria 2020-10-23 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 490 of the ACSF3 protein (p.Glu490Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs147538370, ExAC 0.2%). This variant has been observed in individuals affected with ACSF3-related conditions (PMID: 26827111, 29858964). ClinVar contains an entry for this variant (Variation ID: 377432). 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 ACSF3 protein function. For these reasons, this variant has been classified as Pathogenic.
Pars Genome Lab RCV001245382 SCV001652882 uncertain significance Combined malonic and methylmalonic aciduria 2021-05-18 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV001245382 SCV001781378 uncertain significance Combined malonic and methylmalonic aciduria 2021-07-14 criteria provided, single submitter clinical testing
Natera, Inc. RCV001245382 SCV001457766 uncertain significance Combined malonic and methylmalonic aciduria 2020-01-07 no assertion criteria provided clinical testing

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.