chr4-186076652-G-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_003265.3(TLR3):c.33G>T(p.Trp11Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003265.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TLR3 | NM_003265.3 | c.33G>T | p.Trp11Cys | missense_variant | 2/5 | ENST00000296795.8 | NP_003256.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TLR3 | ENST00000296795.8 | c.33G>T | p.Trp11Cys | missense_variant | 2/5 | 1 | NM_003265.3 | ENSP00000296795 | P1 | |
TLR3 | ENST00000513189.1 | c.33G>T | p.Trp11Cys | missense_variant | 2/5 | 1 | ENSP00000423386 | |||
TLR3 | ENST00000698351.1 | c.33G>T | p.Trp11Cys | missense_variant | 2/5 | ENSP00000513674 | ||||
TLR3 | ENST00000698352.1 | c.33G>T | p.Trp11Cys | missense_variant, NMD_transcript_variant | 2/5 | ENSP00000513675 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152020Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251408Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135870
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727242
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152020Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74242
ClinVar
Submissions by phenotype
Herpes simplex encephalitis, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 10, 2022 | This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 11 of the TLR3 protein (p.Trp11Cys). This variant is present in population databases (rs755127843, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with TLR3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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