rs3135989

Positions:

• chr17-34993124-T-G

Variant summary

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

The NM_013975.4(LIG3):​c.1455+432T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0597 in 152,126 control chromosomes in the GnomAD database, including 408 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 0.060 (408 hom., cov: 33)
• Consequence: LIG3 NM_013975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128

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=-0.58).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG3	NM_013975.4	c.1455+432T>G		intron_variant		ENST00000378526.9	NP_039269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG3	ENST00000378526.9	c.1455+432T>G		intron_variant		1	NM_013975.4	ENSP00000367787.3
LIG3	ENST00000262327.9	c.1455+432T>G		intron_variant		1		ENSP00000262327.4
LIG3	ENST00000585941.5	c.1482+432T>G		intron_variant		1		ENSP00000468479.1
LIG3	ENST00000590630.5	n.448+432T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 9073 AN: 152008 Hom.: 406 Cov.: 33

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.0580

Gnomad FIN AF: 0.0844

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0627

Gnomad OTH AF: 0.0643

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0597 AC: 9076 AN: 152126 Hom.: 408 Cov.: 33 AF XY: 0.0621 AC XY: 4620 AN XY: 74372

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.0507

Gnomad4 SAS AF: 0.0576

Gnomad4 FIN AF: 0.0844

Gnomad4 NFE AF: 0.0627

Gnomad4 OTH AF: 0.0641

Alfa AF: 0.0633 Hom.: 80

Bravo AF: 0.0651

Asia WGS AF: 0.0670 AC: 232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.3
DANN	Benign	0.88

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: rs3135989; hg19: chr17-33320143;