NM_013975.4:c.2113+271C>G

Variant names:

• chr17-34998998-C-G
• rs2074516
• NM_013975.4:c.2113+271C>G

Variant summary

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

The NM_013975.4(LIG3):​c.2113+271C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 504,778 control chromosomes in the GnomAD database, including 14,438 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 0.26 (9351 hom., cov: 32)
  • Exomes 𝑓: 0.14 (5087 hom.)
• Consequence: LIG3 NM_013975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 4 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 = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG3	NM_013975.4	c.2113+271C>G		intron_variant	Intron 14 of 19	ENST00000378526.9	NP_039269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG3	ENST00000378526.9	c.2113+271C>G		intron_variant	Intron 14 of 19	1	NM_013975.4	ENSP00000367787.3
LIG3	ENST00000262327.9	c.2113+271C>G		intron_variant	Intron 14 of 19	1		ENSP00000262327.4
LIG3	ENST00000593099.5	n.1658C>G		non_coding_transcript_exon_variant	Exon 2 of 6	2
LIG3	ENST00000586119.1	n.310+271C>G		intron_variant	Intron 3 of 5	3

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39792 AN: 152016 Hom.: 9311 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.137 AC: 48243 AN: 352644 Hom.: 5087 Cov.: 4 AF XY: 0.135 AC XY: 24566 AN XY: 181850

African (AFR) AF: 0.633 AC: 7055 AN: 11150

American (AMR) AF: 0.118 AC: 1635 AN: 13834

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 2027 AN: 11418

East Asian (EAS) AF: 0.157 AC: 4149 AN: 26476

South Asian (SAS) AF: 0.191 AC: 4951 AN: 25866

European-Finnish (FIN) AF: 0.122 AC: 2838 AN: 23282

Middle Eastern (MID) AF: 0.172 AC: 274 AN: 1592

European-Non Finnish (NFE) AF: 0.101 AC: 21922 AN: 217788

Other (OTH) AF: 0.160 AC: 3392 AN: 21238

GnomAD4 genome AF: 0.262 AC: 39880 AN: 152134 Hom.: 9351 Cov.: 32 AF XY: 0.259 AC XY: 19274 AN XY: 74374

African (AFR) AF: 0.633 AC: 26258 AN: 41470

American (AMR) AF: 0.142 AC: 2170 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 656 AN: 3472

East Asian (EAS) AF: 0.158 AC: 818 AN: 5168

South Asian (SAS) AF: 0.182 AC: 876 AN: 4816

European-Finnish (FIN) AF: 0.136 AC: 1440 AN: 10598

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7081 AN: 67998

Other (OTH) AF: 0.222 AC: 469 AN: 2112

Alfa AF: 0.203 Hom.: 751

Bravo AF: 0.275

Asia WGS AF: 0.238 AC: 829 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.59
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2074516; hg19: chr17-33326017;