rs776064587
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_006859.4(LIAS):c.553_561delATGCCTGAT(p.Met185_Asp187del) variant causes a conservative inframe deletion, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,648 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_006859.4 conservative_inframe_deletion, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LIAS | NM_006859.4 | c.553_561delATGCCTGAT | p.Met185_Asp187del | conservative_inframe_deletion, splice_region_variant | Exon 6 of 11 | ENST00000640888.2 | NP_006850.2 | |
LIAS | NM_001278590.2 | c.553_561delATGCCTGAT | p.Met185_Asp187del | conservative_inframe_deletion, splice_region_variant | Exon 6 of 10 | NP_001265519.1 | ||
LIAS | NM_194451.3 | c.553_561delATGCCTGAT | p.Met185_Asp187del | conservative_inframe_deletion, splice_region_variant | Exon 6 of 10 | NP_919433.1 | ||
LIAS | NM_001363700.2 | c.299+1682_299+1690delATGCCTGAT | intron_variant | Intron 3 of 7 | NP_001350629.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249964Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135114
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460648Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 726612
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Lipoic acid synthetase deficiency Uncertain:1
This variant, c.553_561del, results in the deletion of 3 amino acid(s) of the LIAS protein (p.Met185_Asp187del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with LIAS-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at