17-34983476-C-G

Variant names:

• chr17-34983476-C-G
• NM_013975.4:c.471C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013975.4(LIG3):​c.471C>G​(p.Ile157Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LIG3 NM_013975.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.71

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3377742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG3	NM_013975.4	c.471C>G	p.Ile157Met	missense_variant	Exon 2 of 20	ENST00000378526.9	NP_039269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG3	ENST00000378526.9	c.471C>G	p.Ile157Met	missense_variant	Exon 2 of 20	1	NM_013975.4	ENSP00000367787.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461820 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	0.45
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T;T;.;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Pathogenic	3.3	M;.;M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.7	D;.;D;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D;.;D;.
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.78
MutPred		0.47		Loss of helix (P = 0.0376);.;Loss of helix (P = 0.0376);.;
MVP		0.067
MPC		0.95
ClinPred		0.98	D
GERP RS		-11
Varity_R		0.56
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-33310495;