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

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_013975.4(LIG3):​c.2113+271C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 353,106 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: LIG3 NM_013975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013975.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG3	NM_013975.4	MANE Select	c.2113+271C>T		intron	N/A	NP_039269.2	P49916-1
	LIG3	NM_002311.5		c.2113+271C>T		intron	N/A	NP_002302.2	P49916-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG3	ENST00000378526.9	TSL:1 MANE Select	c.2113+271C>T		intron	N/A	ENSP00000367787.3	P49916-1
	LIG3	ENST00000262327.9	TSL:1	c.2113+271C>T		intron	N/A	ENSP00000262327.4	P49916-2
	LIG3	ENST00000858902.1		c.2113+271C>T		intron	N/A	ENSP00000528961.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000283 AC: 1 AN: 353106 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 182078

African (AFR) AF: 0.00 AC: 0 AN: 11184

American (AMR) AF: 0.00 AC: 0 AN: 13846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11432

East Asian (EAS) AF: 0.00 AC: 0 AN: 26512

South Asian (SAS) AF: 0.0000386 AC: 1 AN: 25932

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1596

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 218004

Other (OTH) AF: 0.00 AC: 0 AN: 21270

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.2
DANN	Benign	0.92
PhyloP100		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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;