19-3600392-G-A

Variant names:

• chr19-3600392-G-A
• rs5745
• NM_001060.6:c.243C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001060.6(TBXA2R):​c.243C>T​(p.Thr81Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 1,613,254 control chromosomes in the GnomAD database, including 7,579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T81T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.10 (892 hom., cov: 32)
  • Exomes 𝑓: 0.094 (6687 hom.)
• Consequence: TBXA2R NM_001060.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.73
• Publications: 13 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)
• bleeding disorder, platelet-type, 13, susceptibility to

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 19-3600392-G-A is Benign according to our data. Variant chr19-3600392-G-A is described in ClinVar as Benign. ClinVar VariationId is 263266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001060.6. 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.243C>T	p.Thr81Thr	synonymous	Exon 2 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.243C>T	p.Thr81Thr	synonymous	Exon 2 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.243C>T	p.Thr81Thr	synonymous	Exon 2 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000589966.1	TSL:1	c.243C>T	p.Thr81Thr	synonymous	Exon 1 of 2	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000411851.3	TSL:2	c.243C>T	p.Thr81Thr	synonymous	Exon 2 of 4	ENSP00000393333.2	P21731-2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15313 AN: 152070 Hom.: 891 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.0829

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.0684

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0976

Gnomad OTH AF: 0.0975

GnomAD2 exomes AF: 0.0814 AC: 20014 AN: 245816 AF XY: 0.0822

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.0505

Gnomad ASJ exome AF: 0.0658

Gnomad EAS exome AF: 0.0264

Gnomad FIN exome AF: 0.0829

Gnomad NFE exome AF: 0.0976

Gnomad OTH exome AF: 0.0907

GnomAD4 exome AF: 0.0936 AC: 136795 AN: 1461066 Hom.: 6687 Cov.: 33 AF XY: 0.0933 AC XY: 67785 AN XY: 726864

African (AFR) AF: 0.140 AC: 4670 AN: 33464

American (AMR) AF: 0.0550 AC: 2460 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0635 AC: 1657 AN: 26108

East Asian (EAS) AF: 0.0166 AC: 660 AN: 39686

South Asian (SAS) AF: 0.0640 AC: 5522 AN: 86254

European-Finnish (FIN) AF: 0.0806 AC: 4270 AN: 53004

Middle Eastern (MID) AF: 0.119 AC: 685 AN: 5762

European-Non Finnish (NFE) AF: 0.100 AC: 111541 AN: 1111724

Other (OTH) AF: 0.0883 AC: 5330 AN: 60360

GnomAD4 genome AF: 0.101 AC: 15317 AN: 152188 Hom.: 892 Cov.: 32 AF XY: 0.0981 AC XY: 7303 AN XY: 74410

African (AFR) AF: 0.135 AC: 5602 AN: 41520

American (AMR) AF: 0.0828 AC: 1266 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0649 AC: 225 AN: 3468

East Asian (EAS) AF: 0.0241 AC: 125 AN: 5182

South Asian (SAS) AF: 0.0682 AC: 329 AN: 4824

European-Finnish (FIN) AF: 0.0778 AC: 824 AN: 10598

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0975 AC: 6631 AN: 67980

Other (OTH) AF: 0.0965 AC: 204 AN: 2114

Alfa AF: 0.0962 Hom.: 393

Bravo AF: 0.102

Asia WGS AF: 0.0450 AC: 157 AN: 3478

EpiCase AF: 0.102

EpiControl AF: 0.106

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.3
DANN	Benign	0.92
PhyloP100		-3.7
PromoterAI		-0.0043	Neutral
Mutation Taster		=100/0	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: rs5745; hg19: chr19-3600390; COSMIC: COSV64343573; COSMIC: COSV64343573;