rs368453789
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The ENST00000424936.6(LIAS):c.397G>A(p.Gly133Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000168 in 1,611,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G133G) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000424936.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIAS | NM_006859.4 | c.393+4G>A | splice_donor_region_variant, intron_variant | ENST00000640888.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIAS | ENST00000640888.2 | c.393+4G>A | splice_donor_region_variant, intron_variant | 1 | NM_006859.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000108 AC: 27AN: 249740Hom.: 0 AF XY: 0.000104 AC XY: 14AN XY: 135012
GnomAD4 exome AF: 0.000169 AC: 247AN: 1459418Hom.: 0 Cov.: 31 AF XY: 0.000158 AC XY: 115AN XY: 725906
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74344
ClinVar
Submissions by phenotype
Lipoic acid synthetase deficiency Uncertain:1Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Brain Gene Registry | - | Variant classified as Uncertain significance and reported on 07-21-2022 by Invitae. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | This sequence change falls in intron 4 of the LIAS gene. It does not directly change the encoded amino acid sequence of the LIAS protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs368453789, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with LIAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 384227). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at