rs367705640
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000018.4(ACADVL):c.121G>A(p.Ala41Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,534,532 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A41A) has been classified as Likely benign.
Frequency
Consequence
NM_000018.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACADVL | NM_000018.4 | c.121G>A | p.Ala41Thr | missense_variant | 2/20 | ENST00000356839.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACADVL | ENST00000356839.10 | c.121G>A | p.Ala41Thr | missense_variant | 2/20 | 1 | NM_000018.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000230 AC: 3AN: 130698Hom.: 0 AF XY: 0.0000140 AC XY: 1AN XY: 71468
GnomAD4 exome AF: 0.0000318 AC: 44AN: 1382184Hom.: 0 Cov.: 35 AF XY: 0.0000293 AC XY: 20AN XY: 681914
GnomAD4 genome ? AF: 0.000217 AC: 33AN: 152348Hom.: 1 Cov.: 33 AF XY: 0.000228 AC XY: 17AN XY: 74506
ClinVar
Submissions by phenotype
Very long chain acyl-CoA dehydrogenase deficiency Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Nov 01, 2019 | The NM_000018.3:c.121G>A (NP_000009.1:p.Ala41Thr) [GRCH38: NC_000017.11:g.7220180G>A] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: BP6 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 41 of the ACADVL protein (p.Ala41Thr). This variant is present in population databases (rs367705640, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with ACADVL-related conditions. ClinVar contains an entry for this variant (Variation ID: 569736). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ACADVL 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, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at