dbSNP rs201087249: TBXA2R:c.*846G>C (chr19-3594842-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_201636.3(TBXA2R):c.1218G>C(p.Lys406Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000717 in 1,536,376 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 1 hom. )

Consequence

TBXA2R
NM_201636.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -0.948

Publications

1 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):

bleeding diathesis due to thromboxane synthesis deficiency
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
qualitative platelet defect
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015095055).

BS2

High AC in GnomAd4 at 101 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201636.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	NM_001060.6	MANE Select	c.*846G>C		3_prime_UTR	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.1218G>C	p.Lys406Asn	missense	Exon 4 of 4	NP_963998.2	P21731-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBXA2R	ENST00000375190.10	TSL:1 MANE Select	c.*846G>C		3_prime_UTR	Exon 3 of 3	ENSP00000364336.4	P21731-3
TBXA2R	ENST00000589966.1	TSL:1	c.*709G>C		3_prime_UTR	Exon 2 of 2	ENSP00000468145.1	K7ER80
TBXA2R	ENST00000411851.3	TSL:2	c.1218G>C	p.Lys406Asn	missense	Exon 4 of 4	ENSP00000393333.2	P21731-2

Frequencies

GnomAD3 genomes

AF:

0.000663

AC:

101

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000445

AC:

AN:

143722

AF XY:

0.000404

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.000939

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000144

Gnomad NFE exome

AF:

0.000613

Gnomad OTH exome

AF:

0.000235

GnomAD4 exome

AF:

0.000723

AC:

1001

AN:

1384014

Hom.:

Cov.:

AF XY:

0.000734

AC XY:

501

AN XY:

682894

show subpopulations

African (AFR)

AF:

0.0000950

AC:

AN:

31574

American (AMR)

AF:

0.000983

AC:

AN:

35610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25174

East Asian (EAS)

AF:

0.00

AC:

AN:

35722

South Asian (SAS)

AF:

0.000114

AC:

AN:

79176

European-Finnish (FIN)

AF:

0.0000576

AC:

AN:

34736

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.000854

AC:

921

AN:

1078466

Other (OTH)

AF:

0.000501

AC:

AN:

57864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

104

157

209

261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

160

200

<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:

0.000663

AC:

101

AN:

152362

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41586

American (AMR)

AF:

0.00373

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000529

AC:

AN:

68042

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000646

Hom.:

Bravo

AF:

0.000695

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.000263

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bleeding disorder, platelet-type, 13, susceptibility to (1)

TBXA2R-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.40

(source)

DANN

Benign

0.97

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.23

M_CAP

Benign

0.014

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.97

PhyloP100

-0.95

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.060

REVEL

Benign

0.0060

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.16

MutPred

0.16

Loss of ubiquitination at K406 (P = 0.0233)

MVP

0.072

MPC

1.4

ClinPred

0.042

GERP RS

-1.6

gMVP

0.19

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over