rs74528014
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006859.4(LIAS):c.376G>A(p.Ala126Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,611,698 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A126A) has been classified as Likely benign.
Frequency
Consequence
NM_006859.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIAS | NM_006859.4 | c.376G>A | p.Ala126Thr | missense_variant | 4/11 | ENST00000640888.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIAS | ENST00000640888.2 | c.376G>A | p.Ala126Thr | missense_variant | 4/11 | 1 | NM_006859.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152080Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248650Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134748
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1459618Hom.: 0 Cov.: 31 AF XY: 0.0000152 AC XY: 11AN XY: 726066
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152080Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74272
ClinVar
Submissions by phenotype
Lipoic acid synthetase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2022 | 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. ClinVar contains an entry for this variant (Variation ID: 586125). This variant has not been reported in the literature in individuals affected with LIAS-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 126 of the LIAS protein (p.Ala126Thr). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 29, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at