rs145535775
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_006859.4(LIAS):c.944G>A(p.Arg315His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,604,120 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R315C) has been classified as Uncertain significance.
Frequency
Consequence
NM_006859.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIAS | NM_006859.4 | c.944G>A | p.Arg315His | missense_variant | 9/11 | ENST00000640888.2 | |
LIAS | NM_001278590.2 | c.815G>A | p.Arg272His | missense_variant | 8/10 | ||
LIAS | NM_194451.3 | c.944G>A | p.Arg315His | missense_variant | 9/10 | ||
LIAS | NM_001363700.2 | c.635G>A | p.Arg212His | missense_variant | 6/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIAS | ENST00000640888.2 | c.944G>A | p.Arg315His | missense_variant | 9/11 | 1 | NM_006859.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000321 AC: 48AN: 149452Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000630 AC: 158AN: 250614Hom.: 0 AF XY: 0.000642 AC XY: 87AN XY: 135516
GnomAD4 exome AF: 0.000317 AC: 461AN: 1454626Hom.: 2 Cov.: 31 AF XY: 0.000336 AC XY: 243AN XY: 724094
GnomAD4 genome ? AF: 0.000321 AC: 48AN: 149494Hom.: 0 Cov.: 32 AF XY: 0.000206 AC XY: 15AN XY: 72810
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 18, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 23, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Lipoic acid synthetase deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at