rs8113293

Variant names:

• chr19-3595035-G-A
• rs8113293
• NM_001060.6:c.*653C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_201636.3(TBXA2R):​c.1025C>T​(p.Thr342Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00786 in 1,096,382 control chromosomes in the GnomAD database, including 434 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T342T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.034 (256 hom., cov: 28)
  • Exomes 𝑓: 0.0038 (178 hom.)
• Consequence: TBXA2R NM_201636.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.66
• Publications: 6 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017550588).
• BP6: Variant 19-3595035-G-A is Benign according to our data. Variant chr19-3595035-G-A is described in ClinVar as Benign. ClinVar VariationId is 1289217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

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.*653C>T		3_prime_UTR	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.1025C>T	p.Thr342Met	missense	Exon 4 of 4	NP_963998.2	P21731-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	ENST00000375190.10	TSL:1 MANE Select	c.*653C>T		3_prime_UTR	Exon 3 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000589966.1	TSL:1	c.*516C>T		3_prime_UTR	Exon 2 of 2	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000411851.3	TSL:2	c.1025C>T	p.Thr342Met	missense	Exon 4 of 4	ENSP00000393333.2	P21731-2

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5033 AN: 149922 Hom.: 251 Cov.: 28

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00946

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.000418

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000325

Gnomad OTH AF: 0.0180

GnomAD2 exomes AF: 0.00757 AC: 1009 AN: 133292 AF XY: 0.00570

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.00660

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000355

Gnomad OTH exome AF: 0.00442

GnomAD4 exome AF: 0.00375 AC: 3550 AN: 946344 Hom.: 178 Cov.: 12 AF XY: 0.00310 AC XY: 1499 AN XY: 483160

African (AFR) AF: 0.124 AC: 2803 AN: 22566

American (AMR) AF: 0.00661 AC: 223 AN: 33750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20862

East Asian (EAS) AF: 0.00 AC: 0 AN: 31614

South Asian (SAS) AF: 0.000481 AC: 34 AN: 70662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29126

Middle Eastern (MID) AF: 0.00750 AC: 24 AN: 3198

European-Non Finnish (NFE) AF: 0.000163 AC: 113 AN: 692946

Other (OTH) AF: 0.00848 AC: 353 AN: 41620

GnomAD4 genome AF: 0.0338 AC: 5065 AN: 150038 Hom.: 256 Cov.: 28 AF XY: 0.0334 AC XY: 2444 AN XY: 73166

African (AFR) AF: 0.120 AC: 4861 AN: 40520

American (AMR) AF: 0.00945 AC: 142 AN: 15032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5120

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10118

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000325 AC: 22 AN: 67724

Other (OTH) AF: 0.0178 AC: 37 AN: 2076

Alfa AF: 0.0191 Hom.: 18

Bravo AF: 0.0391

ExAC AF: 0.00762 AC: 156

Asia WGS AF: 0.00751 AC: 27 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.23
DANN	Benign	0.84
Eigen	Benign	-0.76
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.7
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.013
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.046	D
Vest4		0.047
MVP		0.22
MPC		0.72
ClinPred		0.0066	T
GERP RS		0.23
gMVP		0.19
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8113293; hg19: chr19-3595033; COSMIC: COSV59260736; COSMIC: COSV59260736;