19-48115896-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000234.3(LIG1):c.2653G>A(p.Glu885Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000234.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 251046Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135750
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461716Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727156
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
ClinVar
Submissions by phenotype
not provided Uncertain:1
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with LIG1-related conditions. This variant is present in population databases (rs778165966, ExAC 0.002%). This sequence change replaces glutamic acid with lysine at codon 885 of the LIG1 protein (p.Glu885Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at