ClinVar Miner

Submissions for variant NM_172250.3(MMAA):c.439+4_439+7del (rs1553957939)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000664553 SCV000788536 uncertain significance Vitamin B12-responsive methylmalonic acidemia type cblA 2017-07-27 criteria provided, single submitter clinical testing
Invitae RCV000664553 SCV001577614 likely pathogenic Vitamin B12-responsive methylmalonic acidemia type cblA 2020-07-26 criteria provided, single submitter clinical testing This sequence change falls in intron 2 of the MMAA gene. It does not directly change the encoded amino acid sequence of the MMAA protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with cobalamin A deficiency (PMID: 15523652, 31497484). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.439+1_4del in the literature. ClinVar contains an entry for this variant (Variation ID: 549964). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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.