Variant 4-39459146-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006859.4(LIAS):c.29G>T(p.Arg10Leu) 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 1,461,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10

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 links:

LIAS (HGNC:):

LIAS links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14538193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIAS	NM_006859.4 linkuse as main transcript	c.29G>T	p.Arg10Leu	missense_variant	1/11	ENST00000640888.2	NP_006850.2	O43766-1A0A024R9W0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIAS	ENST00000640888.2 linkuse as main transcript	c.29G>T	p.Arg10Leu	missense_variant	1/11	1	NM_006859.4	ENSP00000492260.1		O43766-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249596

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135162

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.27

T;T;T;.;T;.;.;.;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.91

D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.15

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.9

L;.;.;L;.;.;L;.;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.10

.;.;.;N;N;N;N;.;.

REVEL

Benign

0.13

Sift

Benign

0.046

.;.;.;D;T;T;D;.;.

Sift4G

Benign

0.26

.;.;.;T;D;T;T;.;.

Polyphen

0.020

B;P;B;.;B;.;.;.;.

Vest4

0.28, 0.29, 0.34, 0.35

MutPred

0.40

Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);

MVP

0.82

MPC

0.48

ClinPred

0.47

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.24

gMVP

0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over