Genetic Variant NM_001060.6:c.*715C>T (chr19-3594973-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001060.6(TBXA2R):c.*715C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,531,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

TBXA2R
NM_001060.6 3_prime_UTR

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: -1.27

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.241824).

BS2

High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXA2R	NM_001060.6 link	c.*715C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000375190.10	NP_001051.1	P21731-3Q05C92Q0VAB0
TBXA2R	NM_201636.3 link	c.1087C>T	p.Arg363*	stop_gained	Exon 4 of 4		NP_963998.2	P21731-2Q05C92Q0VAB0
TBXA2R	XM_011528214.3 link	c.*715C>T		3_prime_UTR_variant	Exon 4 of 4		XP_011526516.1	P21731-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBXA2R	ENST00000375190 link	c.*715C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_001060.6	ENSP00000364336.4	P21731-3
TBXA2R	ENST00000589966 link	c.*578C>T		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000468145.1	K7ER80
TBXA2R	ENST00000411851.3 link	c.1087C>T	p.Arg363*	stop_gained	Exon 4 of 4	2		ENSP00000393333.2	P21731-2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000114

AC:

AN:

140504

Hom.:

AF XY:

0.000106

AC XY:

AN XY:

75692

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000266

Gnomad OTH exome

AF:

0.000238

GnomAD4 exome

AF:

0.000194

AC:

267

AN:

1379200

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

122

AN XY:

680770

show subpopulations

Gnomad4 AFR exome

AF:

0.0000318

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000237

Gnomad4 OTH exome

AF:

0.000173

GnomAD4 genome

AF:

0.000112

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000718

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000435

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TBXA2R-related disorder

Uncertain:1

Jul 26, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The TBXA2R c.1087C>T variant is predicted to result in premature protein termination (p.Arg363*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.027% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Few loss-of-function variants have been reported in this gene to date in association with disease (Human Gene Mutation Database; https://www.hgmd.cf.ac.uk/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.29

CADD

Benign

3.6

DANN

Benign

0.87

Eigen

Benign

-0.84

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00057

Vest4

0.081

GERP RS

-1.1

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