chr17-34989518-T-A

Position:

• chr17-34989518-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013975.4(LIG3):​c.744T>A​(p.Ser248Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIG3 NM_013975.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22373408).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIG3	NM_013975.4	c.744T>A	p.Ser248Arg	missense_variant	4/20	ENST00000378526.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG3	ENST00000378526.9	c.744T>A	p.Ser248Arg	missense_variant	4/20	1	NM_013975.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Apr 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.0071	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T;.;T
Eigen	Benign	-0.023
Eigen_PC	Benign	-0.027
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.2	M;.;M;.
MutationTaster	Benign	0.91	D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.9	N;.;N;.
REVEL	Benign	0.099
Sift	Benign	0.037	D;.;D;.
Sift4G	Benign	0.12	T;T;T;D
Polyphen		0.57	P;.;.;.
Vest4		0.48
MutPred		0.28		Loss of phosphorylation at S248 (P = 0.0028);.;Loss of phosphorylation at S248 (P = 0.0028);.;
MVP		0.60
MPC		0.64
ClinPred		0.68	D
GERP RS		-0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.060
gMVP		0.31

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: chr17-33316537;