4-186076652-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_003265.3(TLR3):c.33G>C(p.Trp11Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W11L) has been classified as Uncertain significance.
Frequency
Consequence
NM_003265.3 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLR3 | NM_003265.3 | c.33G>C | p.Trp11Cys | missense_variant | 2/5 | ENST00000296795.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLR3 | ENST00000296795.8 | c.33G>C | p.Trp11Cys | missense_variant | 2/5 | 1 | NM_003265.3 | P1 | |
TLR3 | ENST00000513189.1 | c.33G>C | p.Trp11Cys | missense_variant | 2/5 | 1 | |||
TLR3 | ENST00000698351.1 | c.33G>C | p.Trp11Cys | missense_variant | 2/5 | ||||
TLR3 | ENST00000698352.1 | c.33G>C | p.Trp11Cys | missense_variant, NMD_transcript_variant | 2/5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152020Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251408Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135870
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727242
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152020Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74242
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2022 | The c.33G>C (p.W11C) alteration is located in exon 2 (coding exon 1) of the TLR3 gene. This alteration results from a G to C substitution at nucleotide position 33, causing the tryptophan (W) at amino acid position 11 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Herpes simplex encephalitis, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2023 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with TLR3-related conditions. This variant is present in population databases (rs755127843, gnomAD 0.02%). 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at