19-48161400-T-C

Variant names:

• chr19-48161400-T-C
• rs4987070
• NM_000234.3:c.215A>G

Variant summary

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

The NM_000234.3(LIG1):​c.215A>G​(p.Asp72Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIG1 NM_000234.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.32

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=0.16090786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.215A>G	p.Asp72Gly	missense_variant	Exon 4 of 28	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.215A>G	p.Asp72Gly	missense_variant	Exon 4 of 28	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;.;.;.;.;.
Eigen	Benign	-0.048
Eigen_PC	Benign	0.022
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;D
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.0	M;.;.;M;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.7	D;N;D;.;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.0070	D;D;D;.;.;.
Sift4G	Uncertain	0.013	D;T;D;D;.;.
Polyphen		0.36	B;P;.;.;.;.
Vest4		0.24
MutPred		0.078		Loss of solvent accessibility (P = 0.0477);Loss of solvent accessibility (P = 0.0477);.;Loss of solvent accessibility (P = 0.0477);Loss of solvent accessibility (P = 0.0477);Loss of solvent accessibility (P = 0.0477);
MVP		0.64
MPC		0.37
ClinPred		0.68	D
GERP RS		4.6
Varity_R		0.17
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4987070; hg19: chr19-48664657;