rs35086467

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006859.4(LIAS):c.507A>G(p.Glu169Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 1,614,172 control chromosomes in the GnomAD database, including 6,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 310 hom., cov: 33)

Exomes 𝑓: 0.085 ( 5998 hom. )

Consequence

LIAS
NM_006859.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.678

Publications

8 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 4-39465159-A-G is Benign according to our data. Variant chr4-39465159-A-G is described in ClinVar as Benign. ClinVar VariationId is 138122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.678 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
LIAS	NM_006859.4 link	c.507A>G	p.Glu169Glu	synonymous_variant	Exon 5 of 11	ENST00000640888.2	NP_006850.2
LIAS	NM_001278590.2 link	c.507A>G	p.Glu169Glu	synonymous_variant	Exon 5 of 10		NP_001265519.1
LIAS	NM_194451.3 link	c.507A>G	p.Glu169Glu	synonymous_variant	Exon 5 of 10		NP_919433.1
LIAS	NM_001363700.2 link	c.299+1554A>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 link	c.507A>G	p.Glu169Glu	synonymous_variant	Exon 5 of 11	1	NM_006859.4	ENSP00000492260.1

Frequencies

GnomAD3 genomes

AF:

0.0560

AC:

8530

AN:

152246

Hom.:

311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0158

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0315

Gnomad ASJ

AF:

0.0997

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0503

Gnomad FIN

AF:

0.0578

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0891

Gnomad OTH

AF:

0.0415

GnomAD2 exomes

AF:

0.0605

AC:

15205

AN:

251388

AF XY:

0.0627

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.0285

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0582

Gnomad NFE exome

AF:

0.0851

Gnomad OTH exome

AF:

0.0601

GnomAD4 exome

AF:

0.0848

AC:

124012

AN:

1461808

Hom.:

5998

Cov.:

AF XY:

0.0841

AC XY:

61166

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.0140

AC:

470

AN:

33478

American (AMR)

AF:

0.0294

AC:

1315

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

2679

AN:

26130

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39696

South Asian (SAS)

AF:

0.0547

AC:

4714

AN:

86250

European-Finnish (FIN)

AF:

0.0597

AC:

3189

AN:

53418

Middle Eastern (MID)

AF:

0.0543

AC:

313

AN:

5768

European-Non Finnish (NFE)

AF:

0.0959

AC:

106593

AN:

1111962

Other (OTH)

AF:

0.0784

AC:

4736

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

6276

12553

18829

25106

31382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3950

7900

11850

15800

19750

<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:

0.0560

AC:

8526

AN:

152364

Hom.:

310

Cov.:

AF XY:

0.0537

AC XY:

3998

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.0158

AC:

656

AN:

41590

American (AMR)

AF:

0.0315

AC:

482

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0997

AC:

346

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.0499

AC:

241

AN:

4828

European-Finnish (FIN)

AF:

0.0578

AC:

614

AN:

10624

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0891

AC:

6061

AN:

68030

Other (OTH)

AF:

0.0406

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

435

871

1306

1742

2177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0791

Hom.:

279

Bravo

AF:

0.0530

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0857

EpiControl

AF:

0.0839

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Nov 19, 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. -

Jun 29, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 23, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

-0.59

CADD

Benign

8.8

(source)

DANN

Benign

0.81

PhyloP100

0.68

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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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