rs1057523592
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The ENST00000242592.9(ACADS):āc.461T>Gā(p.Leu154Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,592 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L154F) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000242592.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACADS | NM_000017.4 | c.461T>G | p.Leu154Arg | missense_variant | 4/10 | ENST00000242592.9 | NP_000008.1 | |
ACADS | NM_001302554.2 | c.461T>G | p.Leu154Arg | missense_variant | 4/10 | NP_001289483.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACADS | ENST00000242592.9 | c.461T>G | p.Leu154Arg | missense_variant | 4/10 | 1 | NM_000017.4 | ENSP00000242592 | P1 | |
ACADS | ENST00000411593.2 | c.461T>G | p.Leu154Arg | missense_variant | 4/10 | 2 | ENSP00000401045 | |||
ACADS | ENST00000539690.1 | n.793T>G | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251172Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135804
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461592Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727100
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Deficiency of butyryl-CoA dehydrogenase Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 09, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 154 of the ACADS protein (p.Leu154Arg). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ACADS-related conditions. ClinVar contains an entry for this variant (Variation ID: 389937). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 03, 2016 | The L154R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at