rs554658931
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong
The NM_003265.3(TLR3):c.958G>A(p.Gly320Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,613,724 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G320E) has been classified as Uncertain significance.
Frequency
Consequence
NM_003265.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLR3 | NM_003265.3 | c.958G>A | p.Gly320Arg | missense_variant | 4/5 | ENST00000296795.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLR3 | ENST00000296795.8 | c.958G>A | p.Gly320Arg | missense_variant | 4/5 | 1 | NM_003265.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 152056Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251074Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135824
GnomAD4 exome AF: 0.0000937 AC: 137AN: 1461668Hom.: 0 Cov.: 37 AF XY: 0.0000853 AC XY: 62AN XY: 727146
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 152056Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74254
ClinVar
Submissions by phenotype
Herpes simplex encephalitis, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 21, 2022 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 537919). This variant has not been reported in the literature in individuals affected with TLR3-related conditions. This variant is present in population databases (rs554658931, gnomAD 0.004%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 320 of the TLR3 protein (p.Gly320Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at