LIG1 p.Ala814Ala

Variant names:

• chr19-48117778-G-G
• NM_000234.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr19-48117779--
• chr19-48117779-C-A
• chr19-48117779-C-G
• chr19-48117779-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000234.3(LIG1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: LIG1 NM_000234.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.688
• Publications: 0 publications found

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]

LIG1 Gene-Disease associations (from GenCC):

• immunodeficiency 96

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000234.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	NM_000234.3	MANE Select	c.		exon_region	Exon 26 of 28	NP_000225.1	P18858-1
	LIG1	NM_001320970.2		c.		exon_region	Exon 26 of 28	NP_001307899.1	A0A8V8TQC4
	LIG1	NM_001320971.2		c.		exon_region	Exon 25 of 27	NP_001307900.1	A0A8V8TPH8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	ENST00000263274.12	TSL:1 MANE Select	c.		exon_region	Exon 26 of 28	ENSP00000263274.6	P18858-1
	LIG1	ENST00000594759.5	TSL:1	n.		exon_region	Exon 26 of 28	ENSP00000471380.1	M0R0Q7
	LIG1	ENST00000594759.5	TSL:1	n.		3_prime_UTR	Exon 26 of 28	ENSP00000471380.1	M0R0Q7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-48621035;