rs387906691

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. Variant got 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

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXA2R	NM_001060.6	c.910G>A	p.Asp304Asn	missense_variant	Exon 3 of 3	ENST00000375190.10	NP_001051.1
TBXA2R	NM_201636.3	c.910G>A	p.Asp304Asn	missense_variant	Exon 3 of 4		NP_963998.2
TBXA2R	XM_011528214.3	c.910G>A	p.Asp304Asn	missense_variant	Exon 4 of 4		XP_011526516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXA2R	ENST00000375190.10	c.910G>A	p.Asp304Asn	missense_variant	Exon 3 of 3	1	NM_001060.6	ENSP00000364336.4
TBXA2R	ENST00000589966.1	c.521G>A	p.Gly174Glu	missense_variant	Exon 2 of 2	1		ENSP00000468145.1
TBXA2R	ENST00000411851.3	c.910G>A	p.Asp304Asn	missense_variant	Exon 3 of 4	2		ENSP00000393333.2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Bleeding disorder, platelet-type, 13, susceptibility to Other:1

Jan 14, 2010

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Uncertain	-0.047	T
MutationAssessor	Pathogenic	3.2	M;M
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-4.3	D;D
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.88
MutPred		0.93		Gain of MoRF binding (P = 0.0356);Gain of MoRF binding (P = 0.0356);
MVP		0.86
MPC		1.7
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.79
gMVP		0.77

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

Other links and lift over

dbSNP: rs387906691; hg19: chr19-3595808;