dbSNP rs5758: TBXA2R:c.*654G>T (chr19-3595034-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001060.6(TBXA2R):c.*654G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TBXA2R
NM_001060.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.95

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
TBXA2R	NM_001060.6 link	c.*654G>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000375190.10	NP_001051.1
TBXA2R	NM_201636.3 link	c.1026G>T	p.Thr342Thr	synonymous_variant	Exon 4 of 4		NP_963998.2
TBXA2R	XM_011528214.3 link	c.*654G>T		3_prime_UTR_variant	Exon 4 of 4		XP_011526516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
TBXA2R	ENST00000375190.10 link	c.*654G>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_001060.6	ENSP00000364336.4
TBXA2R	ENST00000589966.1 link	c.*517G>T		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000468145.1
TBXA2R	ENST00000411851.3 link	c.1026G>T	p.Thr342Thr	synonymous_variant	Exon 4 of 4	2		ENSP00000393333.2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

142884

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000102

AC:

AN:

984622

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

500934

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

22448

American (AMR)

AF:

0.00

AC:

AN:

32998

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20860

East Asian (EAS)

AF:

0.00

AC:

AN:

27746

South Asian (SAS)

AF:

0.00

AC:

AN:

70726

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28866

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3268

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

735058

Other (OTH)

AF:

0.0000234

AC:

AN:

42652

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

142966

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69534

African (AFR)

AF:

0.00

AC:

AN:

37538

American (AMR)

AF:

0.00

AC:

AN:

14286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3412

East Asian (EAS)

AF:

0.00

AC:

AN:

4420

South Asian (SAS)

AF:

0.00

AC:

AN:

4378

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66294

Other (OTH)

AF:

0.00

AC:

AN:

1978

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.55

(source)

DANN

Benign

0.44

PhyloP100

-2.0

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over