rs777998984
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000016.6(ACADM):c.426delG(p.Lys143ArgfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,822 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. K142K) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000016.6 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACADM | NM_000016.6 | c.426delG | p.Lys143ArgfsTer7 | frameshift_variant | Exon 6 of 12 | ENST00000370841.9 | NP_000007.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251328Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135842
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461666Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727148
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 30 AF XY: 0.0000538 AC XY: 4AN XY: 74324
ClinVar
Submissions by phenotype
Medium-chain acyl-coenzyme A dehydrogenase deficiency Pathogenic:3
- -
This sequence change creates a premature translational stop signal (p.Lys143Argfs*7) in the ACADM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACADM are known to be pathogenic (PMID: 16121256, 20434380). This variant is present in population databases (rs777998984, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ACADM-related conditions. ClinVar contains an entry for this variant (Variation ID: 203548). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. -
- -
not provided Pathogenic:1
The c.426delG mutation in the ACADM gene causes a frameshift starting with codon Lysine 143, changes this amino acid to an Arginine residue and creates a premature Stop codon at position 7 of the new reading frame, denoted p.Lys143ArgfsX7. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although this mutation has not been previously reported to our knowledge, it is expected to be a pathogenic mutation. The variant is found in ACADM panel(s). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at