chr12-120739362-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000017.4(ACADS):c.1153G>A(p.Ala385Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,612,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000017.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACADS | ENST00000242592.9 | c.1153G>A | p.Ala385Thr | missense_variant | Exon 10 of 10 | 1 | NM_000017.4 | ENSP00000242592.4 | ||
ACADS | ENST00000411593.2 | c.1141G>A | p.Ala381Thr | missense_variant | Exon 10 of 10 | 2 | ENSP00000401045.2 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248180Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135036
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460680Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 726658
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74374
ClinVar
Submissions by phenotype
Deficiency of butyryl-CoA dehydrogenase Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 385 of the ACADS protein (p.Ala385Thr). This variant is present in population databases (no rsID available, gnomAD 0.005%). This missense change has been observed in individual(s) with short chain acyl-CoA dehydrogenase deficiency (PMID: 30612563; Invitae). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACADS protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at