rs1003918

Positions:

• chr17-35005158-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.*652G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 364,218 control chromosomes in the GnomAD database, including 32,137 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 0.38 (12130 hom., cov: 32)
  • Exomes 𝑓: 0.43 (20007 hom.)
• Consequence: LIG3 NM_013975.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG3	NM_013975.4	c.*652G>A		3_prime_UTR_variant	20/20	ENST00000378526.9	NP_039269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG3	ENST00000378526.9	c.*652G>A		3_prime_UTR_variant	20/20	1	NM_013975.4	ENSP00000367787.3

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57680 AN: 151888 Hom.: 12130 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.426 AC: 90462 AN: 212210 Hom.: 20007 Cov.: 0 AF XY: 0.419 AC XY: 49071 AN XY: 117232

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.358

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.379 AC: 57682 AN: 152008 Hom.: 12130 Cov.: 32 AF XY: 0.385 AC XY: 28626 AN XY: 74314

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.385

Alfa AF: 0.434 Hom.: 24952

Bravo AF: 0.359

Asia WGS AF: 0.348 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs1003918; hg19: chr17-33332177;