19-4816328-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_182919.4(TICAM1):c.2050G>A(p.Ala684Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000422 in 1,422,836 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_182919.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TICAM1 | NM_182919.4 | c.2050G>A | p.Ala684Thr | missense_variant | Exon 2 of 2 | ENST00000248244.6 | NP_891549.1 | |
TICAM1 | NM_001385678.1 | c.2008G>A | p.Ala670Thr | missense_variant | Exon 3 of 3 | NP_001372607.1 | ||
TICAM1 | NM_001385679.1 | c.1915G>A | p.Ala639Thr | missense_variant | Exon 2 of 2 | NP_001372608.1 | ||
TICAM1 | NM_001385680.1 | c.1408G>A | p.Ala470Thr | missense_variant | Exon 3 of 3 | NP_001372609.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000138 AC: 3AN: 217584Hom.: 0 AF XY: 0.0000171 AC XY: 2AN XY: 116874
GnomAD4 exome AF: 0.00000422 AC: 6AN: 1422836Hom.: 0 Cov.: 36 AF XY: 0.00000425 AC XY: 3AN XY: 705070
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
PM2_SUP, BP4 -
Herpes simplex encephalitis, susceptibility to, 4 Uncertain:1
This sequence change replaces alanine with threonine at codon 684 of the TICAM1 protein (p.Ala684Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs376421303, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with TICAM1-related conditions. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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