rs115532916
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM5BP4_StrongBP6BS1BS2
The NM_014049.5(ACAD9):c.976G>A(p.Ala326Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0181 in 1,614,070 control chromosomes in the GnomAD database, including 411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A326P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_014049.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACAD9 | NM_014049.5 | c.976G>A | p.Ala326Thr | missense_variant | 10/18 | ENST00000308982.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACAD9 | ENST00000308982.12 | c.976G>A | p.Ala326Thr | missense_variant | 10/18 | 1 | NM_014049.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0172 AC: 2617AN: 152178Hom.: 48 Cov.: 33
GnomAD3 exomes AF: 0.0177 AC: 4446AN: 251452Hom.: 75 AF XY: 0.0182 AC XY: 2478AN XY: 135918
GnomAD4 exome AF: 0.0182 AC: 26626AN: 1461772Hom.: 363 Cov.: 31 AF XY: 0.0183 AC XY: 13297AN XY: 727184
GnomAD4 genome ? AF: 0.0172 AC: 2615AN: 152298Hom.: 48 Cov.: 33 AF XY: 0.0173 AC XY: 1288AN XY: 74470
ClinVar
Submissions by phenotype
Acyl-CoA dehydrogenase 9 deficiency Uncertain:1Benign:4
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 23, 2023 | - - |
Uncertain significance, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | May 31, 2018 | This variant is interpreted as of Uncertain Significance - Conflicting Evidence, for Mitochondrial complex I deficiency due to ACAD9 deficiency, autosomal recessive. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. - |
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 20, 2012 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 10, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 31, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at