rs141687483
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_182919.4(TICAM1):c.269C>A(p.Pro90Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,608,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TICAM1 | NM_182919.4 | c.269C>A | p.Pro90Gln | missense_variant | 2/2 | ENST00000248244.6 | |
TICAM1 | NM_001385678.1 | c.227C>A | p.Pro76Gln | missense_variant | 3/3 | ||
TICAM1 | NM_001385679.1 | c.134C>A | p.Pro45Gln | missense_variant | 2/2 | ||
TICAM1 | NM_001385680.1 | c.-72+275C>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TICAM1 | ENST00000248244.6 | c.269C>A | p.Pro90Gln | missense_variant | 2/2 | 1 | NM_182919.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000247 AC: 6AN: 242834Hom.: 0 AF XY: 0.0000151 AC XY: 2AN XY: 132234
GnomAD4 exome AF: 0.0000117 AC: 17AN: 1455886Hom.: 0 Cov.: 79 AF XY: 0.0000110 AC XY: 8AN XY: 724532
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74344
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.269C>A (p.P90Q) alteration is located in exon 2 (coding exon 1) of the TICAM1 gene. This alteration results from a C to A substitution at nucleotide position 269, causing the proline (P) at amino acid position 90 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, 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 12, 2022 | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 90 of the TICAM1 protein (p.Pro90Gln). This variant is present in population databases (rs141687483, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with TICAM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 473293). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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