Variant chr17-35002030-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013975.4(LIG3):c.2600G>A(p.Arg867His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00485 in 1,609,630 control chromosomes in the GnomAD database, including 330 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.025 ( 168 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 162 hom. )

Consequence

LIG3
NM_013975.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.880

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017380416).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG3	NM_013975.4 linkuse as main transcript	c.2600G>A	p.Arg867His	missense_variant	18/20	ENST00000378526.9	NP_039269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG3	ENST00000378526.9 linkuse as main transcript	c.2600G>A	p.Arg867His	missense_variant	18/20	1	NM_013975.4	ENSP00000367787	P1	P49916-1
LIG3	ENST00000262327.9 linkuse as main transcript	c.2600G>A	p.Arg867His	missense_variant	18/20	1		ENSP00000262327		P49916-2
LIG3	ENST00000593099.5 linkuse as main transcript	n.2453G>A		non_coding_transcript_exon_variant	5/6	2

Frequencies

GnomAD3 genomes

AF:

0.0252

AC:

3829

AN:

152010

Hom.:

169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0869

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0168

GnomAD3 exomes

AF:

0.00679

AC:

1676

AN:

246728

Hom.:

AF XY:

0.00481

AC XY:

643

AN XY:

133650

show subpopulations

Gnomad AFR exome

AF:

0.0898

Gnomad AMR exome

AF:

0.00521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000496

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000170

Gnomad OTH exome

AF:

0.00468

GnomAD4 exome

AF:

0.00272

AC:

3971

AN:

1457502

Hom.:

162

Cov.:

AF XY:

0.00232

AC XY:

1685

AN XY:

725012

show subpopulations

Gnomad4 AFR exome

AF:

0.0927

Gnomad4 AMR exome

AF:

0.00606

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000409

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000166

Gnomad4 OTH exome

AF:

0.00646

GnomAD4 genome

AF:

0.0252

AC:

3837

AN:

152128

Hom.:

168

Cov.:

AF XY:

0.0237

AC XY:

1763

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0868

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0123

Hom.:

Bravo

AF:

0.0297

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0860

AC:

379

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00828

AC:

1005

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.53

DANN

Benign

0.67

DEOGEN2

Uncertain

0.44

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.64

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.60

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.65

N;N

REVEL

Benign

0.037

Sift

Benign

0.29

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.0010

B;.

Vest4

0.040

MVP

0.040

MPC

0.33

ClinPred

0.00073

GERP RS

-7.8

Varity_R

0.020

gMVP

0.18

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

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