Submissions for variant NM_014049.5(ACAD9):c.-44_-41dup

gnomAD frequency: 0.04863  dbSNP: rs387906242

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000001073	SCV000440750	likely benign	Acyl-CoA dehydrogenase 9 deficiency	2016-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000201519	SCV001437357	uncertain significance	not specified	2020-09-23	criteria provided, single submitter	clinical testing	Variant summary: ACAD9 c.-44_-41dupTAAG is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 0.039 in 280626 control chromosomes in the gnomAD database, including 475 homozygotes. The observed variant frequency is approximately 35 fold of the estimated maximal expected allele frequency for a pathogenic variant in ACAD9 causing Mitochondrial Complex I Deficiency, Nuclear Type 20 phenotype (0.0011), strongly suggesting that the variant is benign. c.-44_-41dupTAAG has been reported in the literature in one individual affected with Acyl-Coenzyme dehydrogenase 9 deficiency (He_2007). The report does not provide unequivocal conclusions about association of the variant with Mitochondrial Complex I Deficiency, Nuclear Type 20. He_2007 reports this variant results in a transcriptional defect from patients liver sample and 75% reduction of expression of a reporter gene. One ClinVar submitter (evaluation after 2014) cites the variant as likely benign. Although the allele frequency of this variant suggests it may be benign, the possibility of it being a common low-penetrant pathogenic variant cannot be ruled out. Therefore, this variant was classified as VUS-possibly benign.
Invitae	RCV001515971	SCV001724163	benign	not provided	2023-12-18	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000001073	SCV001737179	likely benign	Acyl-CoA dehydrogenase 9 deficiency	2021-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001515971	SCV001903705	benign	not provided	2018-10-05	criteria provided, single submitter	clinical testing
OMIM	RCV000001073	SCV000021223	pathogenic	Acyl-CoA dehydrogenase 9 deficiency	2007-07-01	no assertion criteria provided	literature only
Natera, Inc.	RCV000001073	SCV001461494	benign	Acyl-CoA dehydrogenase 9 deficiency	2020-09-16	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000201519	SCV001741580	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001515971	SCV001932621	likely benign	not provided		no assertion criteria provided	clinical testing