chr17-34997659-T-C

Position:

• chr17-34997659-T-C

Variant summary

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

The NM_013975.4(LIG3):​c.1824-79T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,013,882 control chromosomes in the GnomAD database, including 1,706 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 0.025 (141 hom., cov: 32)
  • Exomes 𝑓: 0.032 (1565 hom.)
• Consequence: LIG3 NM_013975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.26

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG3	NM_013975.4	c.1824-79T>C		intron_variant		ENST00000378526.9	NP_039269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG3	ENST00000378526.9	c.1824-79T>C		intron_variant		1	NM_013975.4	ENSP00000367787.3

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3763 AN: 152152 Hom.: 142 Cov.: 32

Gnomad AFR AF: 0.00458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0672

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0869

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0268

GnomAD4 exome AF: 0.0318 AC: 27418 AN: 861612 Hom.: 1565 Cov.: 12 AF XY: 0.0331 AC XY: 14933 AN XY: 450914

Gnomad4 AFR exome AF: 0.00407

Gnomad4 AMR exome AF: 0.0754

Gnomad4 ASJ exome AF: 0.0173

Gnomad4 EAS exome AF: 0.232

Gnomad4 SAS exome AF: 0.0748

Gnomad4 FIN exome AF: 0.0186

Gnomad4 NFE exome AF: 0.0133

Gnomad4 OTH exome AF: 0.0262

GnomAD4 genome AF: 0.0247 AC: 3756 AN: 152270 Hom.: 141 Cov.: 32 AF XY: 0.0284 AC XY: 2111 AN XY: 74456

Gnomad4 AFR AF: 0.00457

Gnomad4 AMR AF: 0.0672

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.0857

Gnomad4 FIN AF: 0.0207

Gnomad4 NFE AF: 0.0142

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0197 Hom.: 19

Bravo AF: 0.0271

Asia WGS AF: 0.0860 AC: 298 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0050
DANN	Benign	0.27

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: rs2074517; hg19: chr17-33324678;