rs750168413

Variant names:

• chr4-39465181-C-G
• NM_006859.4:c.529C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-39465181-C-G
• chr4-39465181-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006859.4(LIAS):​c.529C>G​(p.Leu177Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,598 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LIAS NM_006859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.785

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIAS	NM_006859.4	c.529C>G	p.Leu177Val	missense_variant	Exon 5 of 11	ENST00000640888.2	NP_006850.2
LIAS	NM_001278590.2	c.529C>G	p.Leu177Val	missense_variant	Exon 5 of 10		NP_001265519.1
LIAS	NM_194451.3	c.529C>G	p.Leu177Val	missense_variant	Exon 5 of 10		NP_919433.1
LIAS	NM_001363700.2	c.299+1576C>G		intron_variant	Intron 3 of 7		NP_001350629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIAS	ENST00000640888.2	c.529C>G	p.Leu177Val	missense_variant	Exon 5 of 11	1	NM_006859.4	ENSP00000492260.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461598 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727072

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D;.;.;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.68	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.9	L;L;L;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.4	.;N;N;.
REVEL	Uncertain	0.54
Sift	Benign	0.041	.;D;D;.
Sift4G	Benign	0.061	.;T;T;.
Polyphen		0.98	D;.;.;.
Vest4		0.76, 0.64
MutPred		0.64		Gain of phosphorylation at Y174 (P = 0.111);Gain of phosphorylation at Y174 (P = 0.111);Gain of phosphorylation at Y174 (P = 0.111);.;
MVP		0.89
ClinPred		0.81	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-39466801;