4-186083613-C-T
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_003265.3(TLR3):c.1927C>T(p.Arg643Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000972 in 1,605,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R643S) has been classified as Benign.
Frequency
Consequence
NM_003265.3 missense
Scores
Clinical Significance
Conservation
Publications
- immunodeficiency 83, susceptibility to viral infectionsInheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152158Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000575 AC: 14AN: 243514 AF XY: 0.0000455 show subpopulations
GnomAD4 exome AF: 0.000105 AC: 153AN: 1453446Hom.: 0 Cov.: 36 AF XY: 0.0000941 AC XY: 68AN XY: 722290 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74322 show subpopulations
ClinVar
Submissions by phenotype
Herpes simplex encephalitis, susceptibility to, 1 Uncertain:1
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 643 of the TLR3 protein (p.Arg643Cys). This variant is present in population databases (rs73025939, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TLR3-related conditions. ClinVar contains an entry for this variant (Variation ID: 838950). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at