rs796052702

Variant names:

• chr4-39462269-C-A
• rs796052702
• NM_006859.4:c.292C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-39462269-C-A
• chr4-39462269-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_006859.4(LIAS):​c.292C>A​(p.Arg98Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIAS NM_006859.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.778
• Publications: 0 publications found

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]

LIAS Gene-Disease associations (from GenCC):

• lipoic acid synthetase deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP6: Variant 4-39462269-C-A is Benign according to our data. Variant chr4-39462269-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2746571.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.778 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006859.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIAS	NM_006859.4	MANE Select	c.292C>A	p.Arg98Arg	synonymous	Exon 3 of 11	NP_006850.2
	LIAS	NM_001278590.2		c.292C>A	p.Arg98Arg	synonymous	Exon 3 of 10	NP_001265519.1	O43766-3
	LIAS	NM_194451.3		c.292C>A	p.Arg98Arg	synonymous	Exon 3 of 10	NP_919433.1	O43766-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIAS	ENST00000640888.2	TSL:1 MANE Select	c.292C>A	p.Arg98Arg	synonymous	Exon 3 of 11	ENSP00000492260.1	O43766-1
	LIAS	ENST00000424936.6	TSL:1	c.292C>A	p.Arg98Arg	synonymous	Exon 3 of 4	ENSP00000491086.1	Q6P5Q6
	LIAS	ENST00000946185.1		c.286C>A	p.Arg96Arg	synonymous	Exon 3 of 11	ENSP00000616244.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1404200 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 698588

African (AFR) AF: 0.00 AC: 0 AN: 30278

American (AMR) AF: 0.00 AC: 0 AN: 37258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25048

East Asian (EAS) AF: 0.00 AC: 0 AN: 35136

South Asian (SAS) AF: 0.00 AC: 0 AN: 78424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5518

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082296

Other (OTH) AF: 0.00 AC: 0 AN: 57916

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Lipoic acid synthetase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	10
DANN	Benign	0.75
PhyloP100		0.78
PromoterAI		0.0012	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs796052702; hg19: chr4-39463889;