ClinVar Miner

Submissions for variant NM_000016.6(ACADM):c.678A>G (p.Ala226=)

gnomAD frequency: 0.00108  dbSNP: rs2229249
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000211540 SCV000268468 benign Medium-chain acyl-coenzyme A dehydrogenase deficiency 2015-02-20 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000211540 SCV000358940 likely benign Medium-chain acyl-coenzyme A dehydrogenase deficiency 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx RCV000443722 SCV000511933 benign not specified 2015-07-20 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV000211540 SCV000630294 benign Medium-chain acyl-coenzyme A dehydrogenase deficiency 2024-01-30 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758717 SCV000887496 likely benign not provided 2018-01-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000443722 SCV000918375 benign not specified 2017-10-04 criteria provided, single submitter clinical testing Variant summary: The ACADM c.678A>G (p.Ala226Ala) variant involves the alteration of a non-conserved nucleotide causing a synoymous change and 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may alter ESE binding. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1061/277140 control chromosomes, predominantly observed in the Latino subpopulation at a frequency of 0.029955 (1031/34418, 21 homozygotes). This frequency is about 6 times the estimated maximal expected allele frequency of a pathogenic ACADM variant (0.0054233), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. In addition, multiple clinical diagnostic laboratories classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publication. Taken together, this variant is classified as "benign."
Ambry Genetics RCV002363054 SCV002662493 likely benign Inborn genetic diseases 2022-02-17 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.
Breakthrough Genomics, Breakthrough Genomics RCV000758717 SCV005258594 likely benign not provided criteria provided, single submitter not provided
Natera, Inc. RCV000211540 SCV002092844 benign Medium-chain acyl-coenzyme A dehydrogenase deficiency 2017-05-23 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003907788 SCV004724380 benign ACADM-related disorder 2020-04-17 no assertion criteria provided clinical testing This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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.