rs2074522

Positions:

• chr17-35002629-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013975.4(LIG3):​c.2675-39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 1,598,088 control chromosomes in the GnomAD database, including 8,204 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 0.090 (690 hom., cov: 32)
  • Exomes 𝑓: 0.098 (7514 hom.)
• Consequence: LIG3 NM_013975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG3	NM_013975.4	c.2675-39G>A		intron_variant		ENST00000378526.9	NP_039269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG3	ENST00000378526.9	c.2675-39G>A		intron_variant		1	NM_013975.4	ENSP00000367787.3
LIG3	ENST00000262327.9	c.2675-39G>A		intron_variant		1		ENSP00000262327.4
LIG3	ENST00000593099.5	n.2528-39G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0902 AC: 13728 AN: 152124 Hom.: 691 Cov.: 32

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0785

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0490

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0916

GnomAD3 exomes AF: 0.103 AC: 23446 AN: 227626 Hom.: 1344 AF XY: 0.108 AC XY: 13351 AN XY: 123122

Gnomad AFR exome AF: 0.0559

Gnomad AMR exome AF: 0.0819

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.0382

Gnomad SAS exome AF: 0.153

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.112

GnomAD4 exome AF: 0.0979 AC: 141497 AN: 1445846 Hom.: 7514 Cov.: 31 AF XY: 0.100 AC XY: 71928 AN XY: 718186

Gnomad4 AFR exome AF: 0.0567

Gnomad4 AMR exome AF: 0.0808

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.0453

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.128

Gnomad4 NFE exome AF: 0.0940

Gnomad4 OTH exome AF: 0.0987

GnomAD4 genome AF: 0.0901 AC: 13722 AN: 152242 Hom.: 690 Cov.: 32 AF XY: 0.0918 AC XY: 6835 AN XY: 74436

Gnomad4 AFR AF: 0.0578

Gnomad4 AMR AF: 0.0783

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.0487

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.0925

Alfa AF: 0.109 Hom.: 181

Bravo AF: 0.0807

Asia WGS AF: 0.118 AC: 414 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs2074522; hg19: chr17-33329648;