rs5763

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 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=0.013301253).

BP6

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

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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

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

GnomAD3 exomes

AF:

0.0141

AC:

3529

AN:

250862

Hom.:

AF XY:

0.0145

AC XY:

1964

AN XY:

135676

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 SAS exome

AF:

0.00670

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

Gnomad4 AFR exome

AF:

0.00290

Gnomad4 AMR exome

AF:

0.00733

Gnomad4 ASJ exome

AF:

0.0181

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00671

Gnomad4 FIN exome

AF:

0.0117

Gnomad4 NFE exome

AF:

0.0225

Gnomad4 OTH exome

AF:

0.0167

GnomAD4 genome

AF:

0.0141

AC:

2147

AN:

152300

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

991

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00371

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00810

Gnomad4 NFE

AF:

0.0230

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.0202

Hom.:

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

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

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

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