rs869320760
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3PP5
The NM_006859.4(LIAS):c.475_477delinsAAA(p.Glu159Lys) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.
Frequency
Genomes: not found (cov: 32)
Consequence
LIAS
NM_006859.4 missense
NM_006859.4 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.05
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 4-39465127-GAG-AAA is Pathogenic according to our data. Variant chr4-39465127-GAG-AAA is described in ClinVar as [Pathogenic]. Clinvar id is 224601.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIAS | NM_006859.4 | c.475_477delinsAAA | p.Glu159Lys | missense_variant | 5/11 | ENST00000640888.2 | |
LIAS | NM_001278590.2 | c.475_477delinsAAA | p.Glu159Lys | missense_variant | 5/10 | ||
LIAS | NM_194451.3 | c.475_477delinsAAA | p.Glu159Lys | missense_variant | 5/10 | ||
LIAS | NM_001363700.2 | c.299+1522_299+1524delinsAAA | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIAS | ENST00000640888.2 | c.475_477delinsAAA | p.Glu159Lys | missense_variant | 5/11 | 1 | NM_006859.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Lipoic acid synthetase deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 20, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at