ClinVar Miner

Submissions for variant NM_020166.5(MCCC1):c.137-2A>G

gnomAD frequency: 0.00002  dbSNP: rs727504006
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000153469 SCV000229160 pathogenic not provided 2013-11-21 criteria provided, single submitter clinical testing
GeneDx RCV000153469 SCV000680700 pathogenic not provided 2017-12-06 criteria provided, single submitter clinical testing The c.137-2 A>G splice site variant in the MCCC1 gene has been previously reported as homozygous in an asymptomatic individual with 3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency (Stadler et al., 2006). It has also been reported in an assymptomatic infant with positive newborn screening for 3-MCC deficiency in whom a second variant was not identified by sequencing (Morscher et al., 2012). This pathogenic variant destroys the canonical splice acceptor site in intron 2, and is expected to cause abnormal gene splicing. The c.137-2 A>G variant is not observed in large population cohorts (Lek et al., 2016). In summary, we interpret c.137-2 A>G to be a pathogenic variant.
Invitae RCV001850097 SCV002311767 likely pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2023-10-24 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 2 of the MCCC1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MCCC1 are known to be pathogenic (PMID: 11181649, 15359379, 22642865). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 16835865, 22264772). ClinVar contains an entry for this variant (Variation ID: 167274). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001850097 SCV002792992 likely pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2022-04-21 criteria provided, single submitter clinical testing
Baylor Genetics RCV001850097 SCV004194280 pathogenic 3-methylcrotonyl-CoA carboxylase 1 deficiency 2023-06-09 criteria provided, single submitter 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.