Submissions for variant NM_172250.3(MMAA):c.562+1G>A

dbSNP: rs869320656

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000210831	SCV003340192	likely pathogenic	Methylmalonic aciduria, cblA type	2023-07-19	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 225188). This variant has not been reported in the literature in individuals affected with MMAA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 of the MMAA 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 MMAA are known to be pathogenic (PMID: 15523652, 15781192).
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital	RCV000210831	SCV000267130	pathogenic	Methylmalonic aciduria, cblA type	2015-05-18	no assertion criteria provided	research