rs11668325

chr19-48117705-C-T

Variant summary

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

The NM_000234.3(LIG1):c.2516G>A(p.Ser839Asn) 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S839R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LIG1 NM_000234.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.634

Genes affected

LIG1 (HGNC:6598): (DNA ligase 1) This gene encodes a member of the ATP-dependent DNA ligase protein family. The encoded protein functions in DNA replication, recombination, and the base excision repair process. Mutations in this gene that lead to DNA ligase I deficiency result in immunodeficiency and increased sensitivity to DNA-damaging agents. Disruption of this gene may also be associated with a variety of cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

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=0.11638233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIG1	NM_000234.3	c.2516G>A	p.Ser839Asn	missense_variant	26/28	ENST00000263274.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG1	ENST00000263274.12	c.2516G>A	p.Ser839Asn	missense_variant	26/28	1	NM_000234.3	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	17
Dann	Benign	0.96
DEOGEN2	Benign	0.18	T;.;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.11	N
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L;.;.
MutationTaster	Benign	0.94	N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.073
Sift	Benign	0.53	T;T;T
Sift4G	Benign	0.45	T;T;T
Polyphen		0.0030	B;B;.
Vest4		0.28
MutPred		0.41		Gain of catalytic residue at S839 (P = 0.0031);.;.;
MVP		0.53
MPC		0.27
ClinPred		0.21	T
GERP RS		2.2
Varity_R		0.23
gMVP		0.38

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: rs11668325; hg19: chr19-48620962;