rs1052536

Positions:

• chr17-35004556-C-T

Variant summary

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

The NM_013975.4(LIG3):​c.*50C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,480,518 control chromosomes in the GnomAD database, including 143,275 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 0.37 (11705 hom., cov: 31)
  • Exomes 𝑓: 0.44 (131570 hom.)
• Consequence: LIG3 NM_013975.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG3	NM_013975.4	c.*50C>T		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.*50C>T		3_prime_UTR_variant	20/20	1	NM_013975.4	ENSP00000367787	P1
LIG3	ENST00000593099.5	n.4416C>T		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55521 AN: 151802 Hom.: 11707 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.377

GnomAD3 exomes AF: 0.417 AC: 100582 AN: 241450 Hom.: 22174 AF XY: 0.420 AC XY: 54768 AN XY: 130366

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.415

Gnomad ASJ exome AF: 0.347

Gnomad EAS exome AF: 0.304

Gnomad SAS exome AF: 0.370

Gnomad FIN exome AF: 0.570

Gnomad NFE exome AF: 0.464

Gnomad OTH exome AF: 0.416

GnomAD4 exome AF: 0.439 AC: 583420 AN: 1328596 Hom.: 131570 Cov.: 19 AF XY: 0.438 AC XY: 290864 AN XY: 664474

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.241

Gnomad4 SAS exome AF: 0.368

Gnomad4 FIN exome AF: 0.566

Gnomad4 NFE exome AF: 0.460

Gnomad4 OTH exome AF: 0.420

GnomAD4 genome AF: 0.365 AC: 55520 AN: 151922 Hom.: 11705 Cov.: 31 AF XY: 0.371 AC XY: 27526 AN XY: 74222

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.375

Alfa AF: 0.410 Hom.: 6999

Bravo AF: 0.342

Asia WGS AF: 0.345 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.8
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs1052536; hg19: chr17-33331575; COSMIC: COSV52007077; COSMIC: COSV52007077;