19-48123309-G-T

Variant names:

• chr19-48123309-G-T
• rs55950593
• NM_000234.3:c.2014C>A

Variant summary

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

The NM_000234.3(LIG1):​c.2014C>A​(p.Arg672Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,252 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LIG1 NM_000234.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50

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]

ENSG00000269534 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.2014C>A	p.Arg672Ser	missense_variant	Exon 22 of 28	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.2014C>A	p.Arg672Ser	missense_variant	Exon 22 of 28	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250406 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135554

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461252 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726940

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;.;.;.
Eigen	Benign	0.064
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.8	L;.;.;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.4	D;D;D;.
REVEL	Uncertain	0.49
Sift	Benign	0.031	D;T;D;.
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.14	B;D;.;.
Vest4		0.54
MutPred		0.52		Gain of phosphorylation at R672 (P = 0.0684);.;.;Gain of phosphorylation at R672 (P = 0.0684);
MVP		0.68
MPC		0.57
ClinPred		0.93	D
GERP RS		5.1
Varity_R		0.78
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs55950593; hg19: chr19-48626566;