4-186082537-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_003265.3(TLR3):c.851A>T(p.Asn284Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000638 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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 Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251448Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135898
GnomAD4 exome AF: 0.0000670 AC: 98AN: 1461886Hom.: 0 Cov.: 37 AF XY: 0.0000646 AC XY: 47AN XY: 727244
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74362
ClinVar
Submissions by phenotype
Herpes simplex encephalitis, susceptibility to, 1 Uncertain:1
This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 284 of the TLR3 protein (p.Asn284Ile). This variant is present in population databases (rs5743316, gnomAD 0.006%). 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: 848389). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TLR3 function (PMID: 17434873, 21911422). 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