rs387906691

Variant names:

• chr19-3595810-C-T
• rs387906691
• NM_001060.6:c.910G>A
• TBXA2R p.Asp304Asn

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001060.6(TBXA2R):​c.910G>A​(p.Asp304Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBXA2R NM_001060.6 missense
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 7.61
• Publications: 10 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 disorder, platelet-type, 13, susceptibility to

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• 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)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.979

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.910G>A	p.Asp304Asn	missense	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.910G>A	p.Asp304Asn	missense	Exon 3 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.910G>A	p.Asp304Asn	missense	Exon 3 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000589966.1	TSL:1	c.521G>A	p.Gly174Glu	missense	Exon 2 of 2	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000411851.3	TSL:2	c.910G>A	p.Asp304Asn	missense	Exon 3 of 4	ENSP00000393333.2	P21731-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459596 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 726008

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 85878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111338

Other (OTH) AF: 0.00 AC: 0 AN: 60278

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Bleeding disorder, platelet-type, 13, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.72	D
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	-0.047	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		7.6
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.79
gMVP		0.77
Mutation Taster		=14/86	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs387906691;

hg19: chr19-3595808;