chr3-128879647-C-CTAAG
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_014049.5(ACAD9):c.-44_-41dupTAAG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 1,609,038 control chromosomes in the GnomAD database, including 1,480 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_014049.5 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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ACAD9 | NM_014049.5 | c.-44_-41dupTAAG | 5_prime_UTR_variant | Exon 1 of 18 | ENST00000308982.12 | NP_054768.2 | ||
ACAD9 | NM_001410805.1 | c.-319_-316dupTAAG | 5_prime_UTR_variant | Exon 1 of 17 | NP_001397734.1 | |||
ACAD9 | NR_033426.2 | n.29_32dupTAAG | non_coding_transcript_exon_variant | Exon 1 of 18 | ||||
ACAD9 | XR_427367.4 | n.29_32dupTAAG | non_coding_transcript_exon_variant | Exon 1 of 11 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0496 AC: 7542AN: 152108Hom.: 385 Cov.: 32
GnomAD3 exomes AF: 0.0374 AC: 9313AN: 248930Hom.: 395 AF XY: 0.0384 AC XY: 5196AN XY: 135296
GnomAD4 exome AF: 0.0210 AC: 30580AN: 1456812Hom.: 1092 Cov.: 30 AF XY: 0.0229 AC XY: 16587AN XY: 724872
GnomAD4 genome AF: 0.0497 AC: 7560AN: 152226Hom.: 388 Cov.: 32 AF XY: 0.0515 AC XY: 3832AN XY: 74448
ClinVar
Submissions by phenotype
Acyl-CoA dehydrogenase 9 deficiency Pathogenic:1Benign:3
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not provided Benign:3
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not specified Uncertain:1Benign:1
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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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at