rs1553934545
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006859.4(LIAS):āc.683T>Cā(p.Leu228Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
LIAS
NM_006859.4 missense
NM_006859.4 missense
Scores
1
6
8
Clinical Significance
Conservation
PhyloP100: 1.48
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.23869872).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIAS | NM_006859.4 | c.683T>C | p.Leu228Pro | missense_variant | 7/11 | ENST00000640888.2 | |
LIAS | NM_194451.3 | c.683T>C | p.Leu228Pro | missense_variant | 7/10 | ||
LIAS | NM_001363700.2 | c.374T>C | p.Leu125Pro | missense_variant | 4/8 | ||
LIAS | NM_001278590.2 | c.608+2250T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIAS | ENST00000640888.2 | c.683T>C | p.Leu228Pro | missense_variant | 7/11 | 1 | NM_006859.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1455242Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 724248
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1455242
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
724248
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Lipoic acid synthetase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | This sequence change replaces leucine with proline at codon 228 of the LIAS protein (p.Leu228Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with LIAS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;T;.;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;L;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Polyphen
B;P;.;.;.
Vest4
0.55, 0.53
MutPred
Loss of stability (P = 0.0567);.;.;Loss of stability (P = 0.0567);.;
MVP
0.84
MPC
0.80
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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