Genetic Variant LIG3:c.1824-79T>C (chr17-34997659-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013975.4(LIG3):c.1824-79T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,013,882 control chromosomes in the GnomAD database, including 1,706 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.025 ( 141 hom., cov: 32)

Exomes 𝑓: 0.032 ( 1565 hom. )

Consequence

LIG3
NM_013975.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.26

Publications

6 publications found

Variant links:

Genes affected

LIG3 (HGNC:6600): (DNA ligase 3) This gene is a member of the DNA ligase family. Each member of this family encodes a protein that catalyzes the joining of DNA ends but they each have a distinct role in DNA metabolism. The protein encoded by this gene is involved in excision repair and is located in both the mitochondria and nucleus, with translation initiation from the upstream start codon allowing for transport to the mitochondria and translation initiation from a downstream start codon allowing for transport to the nucleus. Additionally, alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

LIG3 Gene-Disease associations (from GenCC):

mitochondrial DNA depletion syndrome 20 (mngie type)
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

LIG3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG3	NM_013975.4 link	c.1824-79T>C		intron_variant	Intron 11 of 19	ENST00000378526.9	NP_039269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG3	ENST00000378526.9 link	c.1824-79T>C		intron_variant	Intron 11 of 19	1	NM_013975.4	ENSP00000367787.3

Frequencies

GnomAD3 genomes

AF:

0.0247

AC:

3763

AN:

152152

Hom.:

142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0672

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.0869

Gnomad FIN

AF:

0.0207

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0142

Gnomad OTH

AF:

0.0268

GnomAD4 exome

AF:

0.0318

AC:

27418

AN:

861612

Hom.:

1565

Cov.:

AF XY:

0.0331

AC XY:

14933

AN XY:

450914

show subpopulations

African (AFR)

AF:

0.00407

AC:

AN:

21862

American (AMR)

AF:

0.0754

AC:

3257

AN:

43196

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

384

AN:

22258

East Asian (EAS)

AF:

0.232

AC:

8484

AN:

36640

South Asian (SAS)

AF:

0.0748

AC:

5534

AN:

74014

European-Finnish (FIN)

AF:

0.0186

AC:

979

AN:

52764

Middle Eastern (MID)

AF:

0.0275

AC:

123

AN:

4470

European-Non Finnish (NFE)

AF:

0.0133

AC:

7506

AN:

565872

Other (OTH)

AF:

0.0262

AC:

1062

AN:

40536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1207

2415

3622

4830

6037

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

336

672

1008

1344

1680

<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:

0.0247

AC:

3756

AN:

152270

Hom.:

141

Cov.:

AF XY:

0.0284

AC XY:

2111

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00457

AC:

190

AN:

41562

American (AMR)

AF:

0.0672

AC:

1028

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3472

East Asian (EAS)

AF:

0.160

AC:

826

AN:

5166

South Asian (SAS)

AF:

0.0857

AC:

413

AN:

4820

European-Finnish (FIN)

AF:

0.0207

AC:

220

AN:

10618

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0142

AC:

966

AN:

68016

Other (OTH)

AF:

0.0256

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

169

338

507

676

845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0166

Hom.:

Bravo

AF:

0.0271

Asia WGS

AF:

0.0860

AC:

298

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0050

(source)

DANN

Benign

0.27

PhyloP100

-3.3

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over