ENST00000589966.1:c.535T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000589966.1(TBXA2R):c.535T>C(p.Tyr179His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,610,200 control chromosomes in the GnomAD database, including 324,213 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 33368 hom., cov: 33)

Exomes 𝑓: 0.62 ( 290845 hom. )

Consequence

TBXA2R
ENST00000589966.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.82

Publications

69 publications found

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 Gene-Disease associations (from GenCC):

qualitative platelet defect
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
bleeding diathesis due to thromboxane synthesis deficiency
Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

TBXA2R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0298587E-6).

BP6

Variant 19-3595796-A-G is Benign according to our data. Variant chr19-3595796-A-G is described in ClinVar as Benign. ClinVar VariationId is 263269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000589966.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	NM_001060.6	MANE Select	c.924T>C	p.Tyr308Tyr	synonymous	Exon 3 of 3	NP_001051.1
	TBXA2R	NM_201636.3		c.924T>C	p.Tyr308Tyr	synonymous	Exon 3 of 4	NP_963998.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TBXA2R	ENST00000589966.1	TSL:1	c.535T>C	p.Tyr179His	missense	Exon 2 of 2	ENSP00000468145.1
TBXA2R	ENST00000375190.10	TSL:1 MANE Select	c.924T>C	p.Tyr308Tyr	synonymous	Exon 3 of 3	ENSP00000364336.4
TBXA2R	ENST00000411851.3	TSL:2	c.924T>C	p.Tyr308Tyr	synonymous	Exon 3 of 4	ENSP00000393333.2

Frequencies

GnomAD3 genomes

AF:

0.649

AC:

98634

AN:

151994

Hom.:

33324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.777

Gnomad AMI

AF:

0.460

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.625

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.462

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.652

Gnomad OTH

AF:

0.655

GnomAD2 exomes

AF:

0.564

AC:

135033

AN:

239524

AF XY:

0.568

show subpopulations

Gnomad AFR exome

AF:

0.787

Gnomad AMR exome

AF:

0.381

Gnomad ASJ exome

AF:

0.621

Gnomad EAS exome

AF:

0.188

Gnomad FIN exome

AF:

0.629

Gnomad NFE exome

AF:

0.654

Gnomad OTH exome

AF:

0.605

GnomAD4 exome

AF:

0.623

AC:

908536

AN:

1458088

Hom.:

290845

Cov.:

103

AF XY:

0.620

AC XY:

449455

AN XY:

725094

show subpopulations

African (AFR)

AF:

0.789

AC:

26403

AN:

33444

American (AMR)

AF:

0.402

AC:

17783

AN:

44238

Ashkenazi Jewish (ASJ)

AF:

0.617

AC:

16070

AN:

26056

East Asian (EAS)

AF:

0.174

AC:

6889

AN:

39598

South Asian (SAS)

AF:

0.481

AC:

41210

AN:

85718

European-Finnish (FIN)

AF:

0.627

AC:

32895

AN:

52440

Middle Eastern (MID)

AF:

0.663

AC:

3822

AN:

5766

European-Non Finnish (NFE)

AF:

0.655

AC:

726969

AN:

1110634

Other (OTH)

AF:

0.606

AC:

36495

AN:

60194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

23760

47519

71279

95038

118798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18768

37536

56304

75072

93840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.649

AC:

98729

AN:

152112

Hom.:

33368

Cov.:

AF XY:

0.642

AC XY:

47749

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.778

AC:

32284

AN:

41508

American (AMR)

AF:

0.535

AC:

8177

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.625

AC:

2168

AN:

3468

East Asian (EAS)

AF:

0.180

AC:

929

AN:

5162

South Asian (SAS)

AF:

0.462

AC:

2229

AN:

4824

European-Finnish (FIN)

AF:

0.627

AC:

6639

AN:

10590

Middle Eastern (MID)

AF:

0.690

AC:

203

AN:

294

European-Non Finnish (NFE)

AF:

0.652

AC:

44302

AN:

67964

Other (OTH)

AF:

0.652

AC:

1380

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1692

3383

5075

6766

8458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.651

Hom.:

70273

Bravo

AF:

0.646

TwinsUK

AF:

0.653

AC:

2423

ALSPAC

AF:

0.653

AC:

2515

ESP6500AA

AF:

0.798

AC:

3482

ESP6500EA

AF:

0.655

AC:

5600

ExAC

AF:

0.569

AC:

68510

Asia WGS

AF:

0.395

AC:

1377

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 28709878, 10830912)

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Benign

9.4

(source)

DANN

Benign

0.80

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0000010

PhyloP100

2.8

Sift4G

Benign

0.20

Vest4

0.22

GERP RS

3.1

Mutation Taster

=88/12

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over