Submissions for variant NM_000018.4(ACADVL):c.663C>T (p.Ser221=)

gnomAD frequency: 0.00116  dbSNP: rs144255994

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen ACADVL Variant Curation Expert Panel, ClinGen	RCV000875845	SCV002769773	likely benign	Very long chain acyl-CoA dehydrogenase deficiency	2022-12-15	reviewed by expert panel	curation	The NM_000018.4(ACADVL):c.663C>T (p.Ser221=) variant is a synonymous (silent) variant that is not predicted by SpliceAI, MaxEntScn and NNSplice to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by phyloP (BP4, BP7). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00353 in African/African American population, which is higher than the ClinGen ACADVL Variant Curation Expert Panel threshold (≥0.0035) for BS1, and therefore meets this criterion (BS1). In summary, this variant meets the criteria to be classified as likely benign for autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: BS1, BP4, BP7.
GeneDx	RCV001703765	SCV000523289	likely benign	not provided	2021-05-26	criteria provided, single submitter	clinical testing
Invitae	RCV000875845	SCV001018321	benign	Very long chain acyl-CoA dehydrogenase deficiency	2024-01-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003972621	SCV004791950	likely benign	ACADVL-related condition	2021-01-05	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).