rs5763

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001061.7(TBXAS1):c.1349C>A(p.Thr450Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 1,613,866 control chromosomes in the GnomAD database, including 337 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 22 hom., cov: 33)

Exomes 𝑓: 0.019 ( 315 hom. )

Consequence

TBXAS1
NM_001061.7 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0840

Publications

25 publications found

Variant links:

Genes affected

TBXAS1 (HGNC:11609): (thromboxane A synthase 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostglandin H2 to thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation. The enzyme plays a role in several pathophysiological processes including hemostasis, cardiovascular disease, and stroke. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

TBXAS1 Gene-Disease associations (from GenCC):

ghosal hematodiaphyseal dysplasia
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet

TBXAS1 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=0.013301253).

BP6

Variant 7-140015845-C-A is Benign according to our data. Variant chr7-140015845-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 287493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0141 (2147/152300) while in subpopulation NFE AF = 0.023 (1563/68026). AF 95% confidence interval is 0.022. There are 22 homozygotes in GnomAd4. There are 991 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXAS1	NM_001061.7 link	c.1349C>A	p.Thr450Asn	missense_variant	Exon 11 of 13	ENST00000448866.7	NP_001052.3	P24557-1Q53F23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXAS1	ENST00000448866.7 link	c.1349C>A	p.Thr450Asn	missense_variant	Exon 11 of 13	1	NM_001061.7	ENSP00000402536.3		P24557-1

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2146

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00372

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0134

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.00810

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0230

Gnomad OTH

AF:

0.0211

GnomAD2 exomes

AF:

0.0141

AC:

3529

AN:

250862

AF XY:

0.0145

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.00691

Gnomad ASJ exome

AF:

0.0180

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.0224

Gnomad OTH exome

AF:

0.0163

GnomAD4 exome

AF:

0.0193

AC:

28250

AN:

1461566

Hom.:

315

Cov.:

AF XY:

0.0191

AC XY:

13903

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.00290

AC:

AN:

33478

American (AMR)

AF:

0.00733

AC:

328

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0181

AC:

472

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00671

AC:

579

AN:

86258

European-Finnish (FIN)

AF:

0.0117

AC:

619

AN:

53106

Middle Eastern (MID)

AF:

0.0165

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0225

AC:

25049

AN:

1112006

Other (OTH)

AF:

0.0167

AC:

1010

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

1676

3352

5028

6704

8380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.0141

AC:

2147

AN:

152300

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

991

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00371

AC:

154

AN:

41546

American (AMR)

AF:

0.0133

AC:

204

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00518

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00810

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0230

AC:

1563

AN:

68026

Other (OTH)

AF:

0.0208

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

115

231

346

462

577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0199

Hom.:

194

Bravo

AF:

0.0139

TwinsUK

AF:

0.0221

AC:

ALSPAC

AF:

0.0218

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0207

AC:

178

ExAC

AF:

0.0147

AC:

1783

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0214

EpiControl

AF:

0.0217

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

May 03, 2016

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.6

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.012

.;T;.;.;T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.81

T;T;.;T;.;T

MetaRNN

Benign

0.013

T;T;T;T;T;T

MetaSVM

Benign

-0.99

PhyloP100

0.084

PrimateAI

Benign

0.28

PROVEAN

Benign

0.23

N;N;.;.;.;.

REVEL

Benign

0.075

Sift

Benign

0.082

T;D;.;.;.;.

Sift4G

Benign

0.091

T;T;.;.;.;.

Polyphen

0.0040

.;.;B;B;.;.

Vest4

0.14

MPC

0.14

ClinPred

0.0022

GERP RS

0.30

gMVP

0.55

Mutation Taster

=98/2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over