Submissions for variant NM_020166.5(MCCC1):c.639+2T>A

gnomAD frequency: 0.00001  dbSNP: rs199914879

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000532293	SCV000656957	pathogenic	3-methylcrotonyl-CoA carboxylase 1 deficiency	2023-06-25	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: 476398). Disruption of this splice site has been observed in individuals with MCC deficiency (PMID: 22642865). This variant is present in population databases (rs199914879, gnomAD 0.02%). This sequence change affects a donor splice site in intron 6 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).
Beijing Key Laboratry for Genetics of Birth Defects, Beijing Children's Hospital	RCV000532293	SCV001739453	pathogenic	3-methylcrotonyl-CoA carboxylase 1 deficiency	2020-02-28	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000532293	SCV004191945	pathogenic	3-methylcrotonyl-CoA carboxylase 1 deficiency	2023-10-21	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001275517	SCV001460702	pathogenic	Methylcrotonyl-CoA carboxylase deficiency	2020-09-16	no assertion criteria provided	clinical testing