12-120738355-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000017.4(ACADS):c.700C>T(p.Arg234Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,178 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 (★★). Synonymous variant affecting the same amino acid position (i.e. R234R) has been classified as Likely benign.
Frequency
Consequence
NM_000017.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACADS | NM_000017.4 | c.700C>T | p.Arg234Trp | missense_variant | 6/10 | ENST00000242592.9 | |
ACADS | NM_001302554.2 | c.688C>T | p.Arg230Trp | missense_variant | 6/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACADS | ENST00000242592.9 | c.700C>T | p.Arg234Trp | missense_variant | 6/10 | 1 | NM_000017.4 | P1 | |
ACADS | ENST00000411593.2 | c.688C>T | p.Arg230Trp | missense_variant | 6/10 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251384Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135882
GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461824Hom.: 0 Cov.: 42 AF XY: 0.0000399 AC XY: 29AN XY: 727210
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74506
ClinVar
Submissions by phenotype
Deficiency of butyryl-CoA dehydrogenase Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 03, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 234 of the ACADS protein (p.Arg234Trp). This variant is present in population databases (rs532174593, gnomAD 0.02%). This missense change has been observed in individual(s) with short-chain acyl-coenzyme A dehydrogenase deficiency (PMID: 27051597). ClinVar contains an entry for this variant (Variation ID: 552250). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jun 01, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at