rs4796030

Variant names:

• chr17-35003131-A-C
• rs4796030
• ENST00000262327.9:c.*83A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000262327.9(LIG3):​c.*83A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 1,588,152 control chromosomes in the GnomAD database, including 265,488 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 0.65 (33590 hom., cov: 30)
  • Exomes 𝑓: 0.56 (231898 hom.)
• Consequence: LIG3 ENST00000262327.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 45 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG3	NM_013975.4	c.2796+342A>C		intron_variant	Intron 19 of 19	ENST00000378526.9	NP_039269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG3	ENST00000262327.9	c.*83A>C		3_prime_UTR_variant	Exon 20 of 20	1		ENSP00000262327.4
LIG3	ENST00000378526.9	c.2796+342A>C		intron_variant	Intron 19 of 19	1	NM_013975.4	ENSP00000367787.3
LIG3	ENST00000592244.1	n.298A>C		non_coding_transcript_exon_variant	Exon 1 of 2	3
LIG3	ENST00000593099.5	n.2991A>C		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98771 AN: 151836 Hom.: 33543 Cov.: 30

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.615

GnomAD4 exome AF: 0.565 AC: 811159 AN: 1436198 Hom.: 231898 Cov.: 39 AF XY: 0.565 AC XY: 402042 AN XY: 712172

African (AFR) AF: 0.866 AC: 28552 AN: 32972

American (AMR) AF: 0.542 AC: 21820 AN: 40276

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 13595 AN: 25554

East Asian (EAS) AF: 0.397 AC: 15221 AN: 38328

South Asian (SAS) AF: 0.576 AC: 48034 AN: 83346

European-Finnish (FIN) AF: 0.694 AC: 36007 AN: 51856

Middle Eastern (MID) AF: 0.538 AC: 3056 AN: 5678

European-Non Finnish (NFE) AF: 0.556 AC: 610688 AN: 1098778

Other (OTH) AF: 0.575 AC: 34186 AN: 59410

GnomAD4 genome AF: 0.651 AC: 98870 AN: 151954 Hom.: 33590 Cov.: 30 AF XY: 0.653 AC XY: 48518 AN XY: 74252

African (AFR) AF: 0.855 AC: 35440 AN: 41450

American (AMR) AF: 0.550 AC: 8402 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1848 AN: 3470

East Asian (EAS) AF: 0.446 AC: 2293 AN: 5138

South Asian (SAS) AF: 0.559 AC: 2690 AN: 4808

European-Finnish (FIN) AF: 0.706 AC: 7466 AN: 10570

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38762 AN: 67944

Other (OTH) AF: 0.618 AC: 1300 AN: 2102

Alfa AF: 0.587 Hom.: 66089

Bravo AF: 0.644

Asia WGS AF: 0.600 AC: 2088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.6
DANN	Benign	0.56
PhyloP100		-0.095
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4796030; hg19: chr17-33330150; COSMIC: COSV107271376; COSMIC: COSV107271376;