rs192016427
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_003265.3(TLR3):c.655G>A(p.Ala219Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,602,432 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_003265.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLR3 | NM_003265.3 | c.655G>A | p.Ala219Thr | missense_variant | 4/5 | ENST00000296795.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLR3 | ENST00000296795.8 | c.655G>A | p.Ala219Thr | missense_variant | 4/5 | 1 | NM_003265.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000406 AC: 6AN: 147792Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250946Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135776
GnomAD4 exome AF: 0.0000351 AC: 51AN: 1454552Hom.: 0 Cov.: 37 AF XY: 0.0000346 AC XY: 25AN XY: 723580
GnomAD4 genome ? AF: 0.0000338 AC: 5AN: 147880Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 1AN XY: 71806
ClinVar
Submissions by phenotype
Herpes simplex encephalitis, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 08, 2023 | This variant is present in population databases (rs192016427, gnomAD 0.02%). 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 567930). This variant has not been reported in the literature in individuals affected with TLR3-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 219 of the TLR3 protein (p.Ala219Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at