4-39462283-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_006859.4(LIAS):c.306C>A(p.Leu102Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 1,515,042 control chromosomes in the GnomAD database, including 1,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 105 hom., cov: 33)

Exomes 𝑓: 0.031 ( 940 hom. )

Consequence

LIAS
NM_006859.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.119

Publications

4 publications found

Variant links:

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: Ambry Genetics, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
Leigh syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

LIAS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 4-39462283-C-A is Benign according to our data. Variant chr4-39462283-C-A is described in ClinVar as Benign. ClinVar VariationId is 138118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIAS	NM_006859.4 link	c.306C>A	p.Leu102Leu	synonymous_variant	Exon 3 of 11	ENST00000640888.2	NP_006850.2	O43766-1A0A024R9W0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIAS	ENST00000640888.2 link	c.306C>A	p.Leu102Leu	synonymous_variant	Exon 3 of 11	1	NM_006859.4	ENSP00000492260.1		O43766-1

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4205

AN:

152060

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00715

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0435

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.0914

Gnomad SAS

AF:

0.0379

Gnomad FIN

AF:

0.00908

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0293

Gnomad OTH

AF:

0.0445

GnomAD2 exomes

AF:

0.0367

AC:

7632

AN:

208012

AF XY:

0.0377

show subpopulations

Gnomad AFR exome

AF:

0.00659

Gnomad AMR exome

AF:

0.0325

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.0849

Gnomad FIN exome

AF:

0.00904

Gnomad NFE exome

AF:

0.0344

Gnomad OTH exome

AF:

0.0579

GnomAD4 exome

AF:

0.0313

AC:

42637

AN:

1362864

Hom.:

940

Cov.:

AF XY:

0.0317

AC XY:

21567

AN XY:

679766

show subpopulations

African (AFR)

AF:

0.00726

AC:

212

AN:

29202

American (AMR)

AF:

0.0347

AC:

1237

AN:

35620

Ashkenazi Jewish (ASJ)

AF:

0.0996

AC:

2448

AN:

24568

East Asian (EAS)

AF:

0.103

AC:

3530

AN:

34420

South Asian (SAS)

AF:

0.0334

AC:

2518

AN:

75396

European-Finnish (FIN)

AF:

0.0109

AC:

565

AN:

52020

Middle Eastern (MID)

AF:

0.101

AC:

542

AN:

5382

European-Non Finnish (NFE)

AF:

0.0278

AC:

29217

AN:

1049922

Other (OTH)

AF:

0.0420

AC:

2368

AN:

56334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

1579

3159

4738

6318

7897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1126

2252

3378

4504

5630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0277

AC:

4214

AN:

152178

Hom.:

105

Cov.:

AF XY:

0.0275

AC XY:

2047

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00713

AC:

296

AN:

41536

American (AMR)

AF:

0.0434

AC:

664

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

371

AN:

3468

East Asian (EAS)

AF:

0.0920

AC:

476

AN:

5174

South Asian (SAS)

AF:

0.0377

AC:

182

AN:

4828

European-Finnish (FIN)

AF:

0.00908

AC:

AN:

10572

Middle Eastern (MID)

AF:

0.110

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0293

AC:

1994

AN:

67994

Other (OTH)

AF:

0.0483

AC:

102

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

205

410

614

819

1024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0334

Hom.:

Bravo

AF:

0.0306

Asia WGS

AF:

0.0700

AC:

242

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 19, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Nov 05, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Lipoic acid synthetase deficiency

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

4.4

(source)

DANN

Benign

0.78

PhyloP100

-0.12

PromoterAI

-0.0020

Neutral

(source)

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over