chr19-3595721-C-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001060.6(TBXA2R):c.999G>T(p.Gln333His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000788 in 1,599,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001060.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBXA2R | NM_001060.6 | c.999G>T | p.Gln333His | missense_variant | 3/3 | ENST00000375190.10 | |
TBXA2R | XM_011528214.3 | c.999G>T | p.Gln333His | missense_variant | 4/4 | ||
TBXA2R | NM_201636.3 | c.983+16G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBXA2R | ENST00000375190.10 | c.999G>T | p.Gln333His | missense_variant | 3/3 | 1 | NM_001060.6 | P1 | |
TBXA2R | ENST00000589966.1 | c.610G>T | p.Ala204Ser | missense_variant | 2/2 | 1 | |||
TBXA2R | ENST00000411851.3 | c.983+16G>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152262Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000184 AC: 4AN: 217422Hom.: 0 AF XY: 0.0000169 AC XY: 2AN XY: 118344
GnomAD4 exome AF: 0.0000850 AC: 123AN: 1446912Hom.: 0 Cov.: 67 AF XY: 0.0000821 AC XY: 59AN XY: 718290
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152262Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74388
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 01, 2023 | Variant summary: TBXA2R c.999G>T (p.Gln333His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.8e-05 in 217422 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.999G>T in individuals affected with Bleeding Diathesis Due To Thromboxane Synthesis Deficiency or other TBXA2R-related disorders and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has provided a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 13, 2022 | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with TBXA2R-related conditions. This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 333 of the TBXA2R protein (p.Gln333His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at