Variant 19-3594847-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001060.6(TBXA2R):c.*841A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,536,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000094 ( 0 hom. )

Consequence

TBXA2R
NM_001060.6 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0240

Variant links:

Genes affected

TBXA2R (HGNC:11608): (thromboxane A2 receptor) This gene encodes a member of the G protein-coupled receptor family. The protein interacts with thromboxane A2 to induce platelet aggregation and regulate hemostasis. A mutation in this gene results in a bleeding disorder. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

TBXA2R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08223149).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TBXA2R	NM_001060.6 linkuse as main transcript	c.*841A>G		3_prime_UTR_variant	3/3	ENST00000375190.10	NP_001051.1
TBXA2R	NM_201636.3 linkuse as main transcript	c.1213A>G	p.Arg405Gly	missense_variant	4/4		NP_963998.2
TBXA2R	XM_011528214.3 linkuse as main transcript	c.*841A>G		3_prime_UTR_variant	4/4		XP_011526516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXA2R	ENST00000375190.10 linkuse as main transcript	c.*841A>G		3_prime_UTR_variant	3/3	1	NM_001060.6	ENSP00000364336	P1	P21731-3
TBXA2R	ENST00000589966.1 linkuse as main transcript	c.*704A>G		3_prime_UTR_variant	2/2	1		ENSP00000468145
TBXA2R	ENST00000411851.3 linkuse as main transcript	c.1213A>G	p.Arg405Gly	missense_variant	4/4	2		ENSP00000393333		P21731-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000624

AC:

AN:

144146

Hom.:

AF XY:

0.0000519

AC XY:

AN XY:

77022

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000939

AC:

AN:

1384438

Hom.:

Cov.:

AF XY:

0.00000439

AC XY:

AN XY:

683118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000364

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152382

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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

Nov 07, 2023

Variant summary: TBXA2R c.*841A>G is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 6.2e-05 in 144146 control chromosomes. 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.*841A>G in individuals affected with Bleeding Diathesis Due To Thromboxane Synthesis Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. This variant is also observed as c.1213A>G (p.Arg405Gly) in NM_001060.6. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.61

CADD

Benign

2.2

DANN

Benign

0.95

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.26

M_CAP

Benign

0.0059

MetaRNN

Benign

0.082

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.020

REVEL

Benign

0.015

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.13

MutPred

0.20

Gain of relative solvent accessibility (P = 0.0275);

MVP

0.30

MPC

1.1

ClinPred

0.035

GERP RS

-0.43

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over