4-39471242-G-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006859.4(LIAS):c.890G>T(p.Arg297Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Consequence
LIAS
NM_006859.4 missense
NM_006859.4 missense
Scores
11
7
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 9.36
Genes affected
LIAS (HGNC:16429): (lipoic acid synthetase) The protein encoded by this gene belongs to the biotin and lipoic acid synthetases family. Localized in the mitochondrion, this iron-sulfur enzyme catalyzes the final step in the de novo pathway for the biosynthesis of lipoic acid, a potent antioxidant. The deficient expression of this enzyme has been linked to conditions such as diabetes, atherosclerosis and neonatal-onset epilepsy. Alternative splicing occurs at this locus, and several transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.878
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LIAS | NM_006859.4 | c.890G>T | p.Arg297Leu | missense_variant | Exon 9 of 11 | ENST00000640888.2 | NP_006850.2 | |
LIAS | NM_001278590.2 | c.761G>T | p.Arg254Leu | missense_variant | Exon 8 of 10 | NP_001265519.1 | ||
LIAS | NM_194451.3 | c.890G>T | p.Arg297Leu | missense_variant | Exon 9 of 10 | NP_919433.1 | ||
LIAS | NM_001363700.2 | c.581G>T | p.Arg194Leu | missense_variant | Exon 6 of 8 | NP_001350629.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;T;.;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.;M;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;D;D;.;D;.;.;.
REVEL
Pathogenic
Sift
Uncertain
.;D;D;.;D;.;.;.
Sift4G
Uncertain
.;D;D;.;D;.;.;.
Polyphen
D;.;D;.;.;.;.;.
Vest4
0.89, 0.89, 0.91
MutPred
Loss of ubiquitination at K294 (P = 0.0578);.;.;.;Loss of ubiquitination at K294 (P = 0.0578);.;.;.;
MVP
0.94
MPC
1.3
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at