Variant chr19-3595925-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000589966.1(TBXA2R):c.406C>T(p.Arg136Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,590,290 control chromosomes in the GnomAD database, including 29,341 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R136H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.16 ( 2815 hom., cov: 32)

Exomes 𝑓: 0.17 ( 26526 hom. )

Consequence

TBXA2R
ENST00000589966.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.249

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3116118E-5).

BP6

Variant 19-3595925-G-A is Benign according to our data. Variant chr19-3595925-G-A is described in ClinVar as [Benign]. Clinvar id is 263268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TBXA2R	NM_001060.6 linkuse as main transcript	c.795C>T	p.Ile265=	synonymous_variant	3/3	ENST00000375190.10
TBXA2R	NM_201636.3 linkuse as main transcript	c.795C>T	p.Ile265=	synonymous_variant	3/4
TBXA2R	XM_011528214.3 linkuse as main transcript	c.795C>T	p.Ile265=	synonymous_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXA2R	ENST00000589966.1 linkuse as main transcript	c.406C>T	p.Arg136Cys	missense_variant	2/2	1
TBXA2R	ENST00000375190.10 linkuse as main transcript	c.795C>T	p.Ile265=	synonymous_variant	3/3	1	NM_001060.6	P1	P21731-3
TBXA2R	ENST00000411851.3 linkuse as main transcript	c.795C>T	p.Ile265=	synonymous_variant	3/4	2			P21731-2

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23706

AN:

152060

Hom.:

2809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0592

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.607

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.197

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.168

GnomAD3 exomes

AF:

0.223

AC:

45836

AN:

205122

Hom.:

7117

AF XY:

0.216

AC XY:

24087

AN XY:

111744

show subpopulations

Gnomad AFR exome

AF:

0.0512

Gnomad AMR exome

AF:

0.380

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.605

Gnomad SAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.145

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.170

AC:

244978

AN:

1438112

Hom.:

26526

Cov.:

AF XY:

0.171

AC XY:

122204

AN XY:

713250

show subpopulations

Gnomad4 AFR exome

AF:

0.0522

Gnomad4 AMR exome

AF:

0.359

Gnomad4 ASJ exome

AF:

0.247

Gnomad4 EAS exome

AF:

0.625

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.147

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.186

GnomAD4 genome

AF:

0.156

AC:

23712

AN:

152178

Hom.:

2815

Cov.:

AF XY:

0.160

AC XY:

11904

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0590

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.248

Gnomad4 EAS

AF:

0.607

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.148

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.166

Alfa

AF:

0.156

Hom.:

1113

Bravo

AF:

0.166

TwinsUK

AF:

0.142

AC:

526

ALSPAC

AF:

0.153

AC:

588

ESP6500AA

AF:

0.0552

AC:

226

ESP6500EA

AF:

0.153

AC:

1276

ExAC

AF:

0.192

AC:

22779

Asia WGS

AF:

0.302

AC:

1049

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	This variant is associated with the following publications: (PMID: 11922633, 23517037) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

6.4

DANN

Benign

0.87

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.41

MetaRNN

Benign

0.000013

MutationTaster

Benign

0.00077

P;P;P

Sift4G

Benign

0.087

Vest4

0.20

GERP RS

-0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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