Submissions for variant NM_000017.4(ACADS):c.795+1G>A

dbSNP: rs752978753

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001555681	SCV001777135	likely pathogenic	not provided	2019-11-08	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in an in-frame deletion of a critical region; Not observed in large population cohorts (Lek et al., 2016)
Genetic Services Laboratory, University of Chicago	RCV001555681	SCV002064495	pathogenic	not provided	2017-07-24	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002032611	SCV002286827	likely pathogenic	Deficiency of butyryl-CoA dehydrogenase	2022-09-19	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: 1193318). This variant has not been reported in the literature in individuals affected with ACADS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 6 of the ACADS 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 ACADS are known to be pathogenic (PMID: 12736383, 18523805).