11-126293085-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_148910.3(TIRAP):c.676C>T(p.Arg226Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_148910.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TIRAP | NM_001318777.2 | c.646+30C>T | intron_variant | ENST00000392679.6 | NP_001305706.1 | |||
TIRAP | NM_001318776.2 | c.676C>T | p.Arg226Trp | missense_variant | 4/4 | NP_001305705.1 | ||
TIRAP | NM_148910.3 | c.676C>T | p.Arg226Trp | missense_variant | 5/5 | NP_683708.1 | ||
TIRAP | NM_001039661.2 | c.646+30C>T | intron_variant | NP_001034750.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000362 AC: 9AN: 248430Hom.: 0 AF XY: 0.0000445 AC XY: 6AN XY: 134868
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461458Hom.: 0 Cov.: 34 AF XY: 0.0000193 AC XY: 14AN XY: 727054
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74344
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2024 | The c.676C>T (p.R226W) alteration is located in exon 5 (coding exon 2) of the TIRAP gene. This alteration results from a C to T substitution at nucleotide position 676, causing the arginine (R) at amino acid position 226 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at