4-186082643-C-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_003265.3(TLR3):c.957C>A(p.His319Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000861 in 1,613,758 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. H319H) has been classified as Likely benign.
Frequency
Consequence
NM_003265.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLR3 | NM_003265.3 | c.957C>A | p.His319Gln | missense_variant | 4/5 | ENST00000296795.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLR3 | ENST00000296795.8 | c.957C>A | p.His319Gln | missense_variant | 4/5 | 1 | NM_003265.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000143 AC: 36AN: 251012Hom.: 1 AF XY: 0.000133 AC XY: 18AN XY: 135816
GnomAD4 exome AF: 0.0000883 AC: 129AN: 1461634Hom.: 2 Cov.: 37 AF XY: 0.0000894 AC XY: 65AN XY: 727142
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74290
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 21, 2022 | The c.957C>A (p.H319Q) alteration is located in exon 4 (coding exon 3) of the TLR3 gene. This alteration results from a C to A substitution at nucleotide position 957, causing the histidine (H) at amino acid position 319 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Herpes simplex encephalitis, susceptibility to, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 12, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at