Submissions for variant NM_172250.3(MMAA):c.733+1G>A

gnomAD frequency: 0.00001  dbSNP: rs779939886

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
University Children's Hospital, University of Zurich	RCV000203316	SCV000606790	pathogenic	Methylmalonic aciduria, cblA type		criteria provided, single submitter	clinical testing
Counsyl	RCV000203316	SCV000790060	likely pathogenic	Methylmalonic aciduria, cblA type	2017-03-02	criteria provided, single submitter	clinical testing
Invitae	RCV000203316	SCV001396170	pathogenic	Methylmalonic aciduria, cblA type	2023-09-13	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as 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: 218978). Disruption of this splice site has been observed in individuals with methylmalonic aciduria (PMID: 15523652, 27858373, 28497574). This variant is present in population databases (rs779939886, gnomAD 0.0009%). This sequence change affects a donor splice site in intron 4 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).
GeneReviews	RCV000203316	SCV000258480	not provided	Methylmalonic aciduria, cblA type		no assertion provided	literature only
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001729456	SCV001979502	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001729456	SCV001980010	pathogenic	not provided		no assertion criteria provided	clinical testing