NM_000016.6:c.957_958delAT
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000016.6(ACADM):c.957_958delAT(p.Ser320IlefsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
ACADM
NM_000016.6 frameshift
NM_000016.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.36
Publications
0 publications found
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]
ACADM Gene-Disease associations (from GenCC):
- medium chain acyl-CoA dehydrogenase deficiencyInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-75761130-AAT-A is Pathogenic according to our data. Variant chr1-75761130-AAT-A is described in ClinVar as Pathogenic. ClinVar VariationId is 371224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000016.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ACADM | MANE Select | c.957_958delAT | p.Ser320IlefsTer5 | frameshift | Exon 11 of 12 | NP_000007.1 | A0A0S2Z366 | ||
| ACADM | c.1056_1057delAT | p.Ser353IlefsTer5 | frameshift | Exon 12 of 13 | NP_001272972.1 | Q5T4U5 | |||
| ACADM | c.969_970delAT | p.Ser324IlefsTer5 | frameshift | Exon 11 of 12 | NP_001120800.1 | P11310-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ACADM | TSL:1 MANE Select | c.957_958delAT | p.Ser320IlefsTer5 | frameshift | Exon 11 of 12 | ENSP00000359878.5 | P11310-1 | ||
| ACADM | TSL:1 | c.1056_1057delAT | p.Ser353IlefsTer5 | frameshift | Exon 12 of 13 | ENSP00000359871.5 | Q5T4U5 | ||
| ACADM | TSL:1 | c.969_970delAT | p.Ser324IlefsTer5 | frameshift | Exon 11 of 12 | ENSP00000409612.2 | P11310-2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461626Hom.: 0 AF XY: 0.00000550 AC XY: 4AN XY: 727134 show subpopulations
GnomAD4 exome
AF:
AC:
7
AN:
1461626
Hom.:
AF XY:
AC XY:
4
AN XY:
727134
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39684
South Asian (SAS)
AF:
AC:
0
AN:
86246
European-Finnish (FIN)
AF:
AC:
0
AN:
53372
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
7
AN:
1111834
Other (OTH)
AF:
AC:
0
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.418
Heterozygous variant carriers
0
1
1
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
4
-
-
Medium-chain acyl-coenzyme A dehydrogenase deficiency (4)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Publications
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