rs201996792
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_006859.4(LIAS):āc.60T>Cā(p.Tyr20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000094 in 1,574,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00011 ( 0 hom., cov: 33)
Exomes š: 0.000092 ( 0 hom. )
Consequence
LIAS
NM_006859.4 synonymous
NM_006859.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.567
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant 4-39460804-T-C is Benign according to our data. Variant chr4-39460804-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 472880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-39460804-T-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.567 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LIAS | NM_006859.4 | c.60T>C | p.Tyr20= | synonymous_variant | 2/11 | ENST00000640888.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LIAS | ENST00000640888.2 | c.60T>C | p.Tyr20= | synonymous_variant | 2/11 | 1 | NM_006859.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152178Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000947 AC: 21AN: 221864Hom.: 0 AF XY: 0.0000665 AC XY: 8AN XY: 120348
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GnomAD4 exome AF: 0.0000921 AC: 131AN: 1422362Hom.: 0 Cov.: 30 AF XY: 0.0000878 AC XY: 62AN XY: 706170
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GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152296Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6AN XY: 74476
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Lipoic acid synthetase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 11, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at