13-108209662-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_206937.2(LIG4):c.1607G>A(p.Ser536Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,614,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_206937.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LIG4 | NM_206937.2 | c.1607G>A | p.Ser536Asn | missense_variant | Exon 3 of 3 | ENST00000442234.6 | NP_996820.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000107 AC: 27AN: 251328Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135882
GnomAD4 exome AF: 0.0000725 AC: 106AN: 1461868Hom.: 0 Cov.: 34 AF XY: 0.0000839 AC XY: 61AN XY: 727236
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74476
ClinVar
Submissions by phenotype
DNA ligase IV deficiency Uncertain:2
This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 536 of the LIG4 protein (p.Ser536Asn). This variant is present in population databases (rs552242241, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with LIG4-related conditions. ClinVar contains an entry for this variant (Variation ID: 581350). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LIG4 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
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not specified Uncertain:1
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not provided Uncertain:1
BP4 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at