Submissions for variant NM_000017.4(ACADS):c.1054G>A (p.Ala352Thr)

dbSNP: rs202078273

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000498121	SCV000589916	uncertain significance	not provided	2017-06-09	criteria provided, single submitter	clinical testing	The A352T variant was identified in a patient with short chain acyl-CoA dehydrogenase (SCAD) deficiency who was homozygous for both A352T and for the common G209S variant which is a well studied variant known to confer susceptibility to develop SCAD deficiency (Rodolfo et al. 2016). The A352T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A352T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether the A352T variant is a pathogenic variant or a rare benign variant.
Counsyl	RCV000673648	SCV000798875	uncertain significance	Deficiency of butyryl-CoA dehydrogenase	2018-03-27	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000673648	SCV001543730	likely pathogenic	Deficiency of butyryl-CoA dehydrogenase	2024-01-04	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 352 of the ACADS protein (p.Ala352Thr). This variant is present in population databases (rs202078273, gnomAD 0.004%). This missense change has been observed in individuals with biochemical features of short chain acyl-CoA dehydrogenase (SCAD) deficiency (PMID: 27051597, 30612563). ClinVar contains an entry for this variant (Variation ID: 432218). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACADS protein function with a positive predictive value of 95%. 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.
Genome-Nilou Lab	RCV000673648	SCV002033271	uncertain significance	Deficiency of butyryl-CoA dehydrogenase	2021-11-07	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000673648	SCV002783195	uncertain significance	Deficiency of butyryl-CoA dehydrogenase	2021-08-30	criteria provided, single submitter	clinical testing
Neonatal Disease Screening Center, Medical Genetics Center, Huaihua City Maternal and Child Health Care Hospital	RCV000673648	SCV004800891	pathogenic	Deficiency of butyryl-CoA dehydrogenase		no assertion criteria provided	clinical testing	PM2_P+PM3_VS+PP3+PP4