rs74090726
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000016.6(ACADM):āc.351A>Cā(p.Thr117Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 1,613,988 control chromosomes in the GnomAD database, including 1,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.049 ( 276 hom., cov: 33)
Exomes š: 0.029 ( 865 hom. )
Consequence
ACADM
NM_000016.6 synonymous
NM_000016.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.388
Genes affected
ACADM (HGNC:89): (acyl-CoA dehydrogenase medium chain) This gene encodes the medium-chain specific (C4 to C12 straight chain) acyl-Coenzyme A dehydrogenase. The homotetramer enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. Defects in this gene cause medium-chain acyl-CoA dehydrogenase deficiency, a disease characterized by hepatic dysfunction, fasting hypoglycemia, and encephalopathy, which can result in infantile death. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 1-75733592-A-C is Benign according to our data. Variant chr1-75733592-A-C is described in ClinVar as [Benign]. Clinvar id is 92263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-75733592-A-C is described in Lovd as [Likely_benign]. Variant chr1-75733592-A-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACADM | NM_000016.6 | c.351A>C | p.Thr117Thr | synonymous_variant | 5/12 | ENST00000370841.9 | NP_000007.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACADM | ENST00000370841.9 | c.351A>C | p.Thr117Thr | synonymous_variant | 5/12 | 1 | NM_000016.6 | ENSP00000359878.5 |
Frequencies
GnomAD3 genomes AF: 0.0489 AC: 7442AN: 152150Hom.: 274 Cov.: 33
GnomAD3 genomes
AF:
AC:
7442
AN:
152150
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0269 AC: 6760AN: 251442Hom.: 153 AF XY: 0.0250 AC XY: 3403AN XY: 135896
GnomAD3 exomes
AF:
AC:
6760
AN:
251442
Hom.:
AF XY:
AC XY:
3403
AN XY:
135896
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0293 AC: 42870AN: 1461720Hom.: 865 Cov.: 31 AF XY: 0.0284 AC XY: 20637AN XY: 727168
GnomAD4 exome
AF:
AC:
42870
AN:
1461720
Hom.:
Cov.:
31
AF XY:
AC XY:
20637
AN XY:
727168
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0490 AC: 7458AN: 152268Hom.: 276 Cov.: 33 AF XY: 0.0474 AC XY: 3526AN XY: 74450
GnomAD4 genome
AF:
AC:
7458
AN:
152268
Hom.:
Cov.:
33
AF XY:
AC XY:
3526
AN XY:
74450
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
37
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:10Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Medium-chain acyl-coenzyme A dehydrogenase deficiency Benign:5
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 28, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
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 | Counsyl | Jan 19, 2018 | - - |
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 29, 2013 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 24, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 25, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
MCAD DEFICIENCY, MODIFIER OF Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Mar 01, 2007 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at