rs397514542

chr19-3599913-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001060.6(TBXA2R):c.722T>G(p.Val241Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBXA2R NM_001060.6 missense
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 7.21

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBXA2R	NM_001060.6	c.722T>G	p.Val241Gly	missense_variant	2/3	ENST00000375190.10
TBXA2R	NM_201636.3	c.722T>G	p.Val241Gly	missense_variant	2/4
TBXA2R	XM_011528214.3	c.722T>G	p.Val241Gly	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXA2R	ENST00000375190.10	c.722T>G	p.Val241Gly	missense_variant	2/3	1	NM_001060.6	P1
TBXA2R	ENST00000589966.1	c.397+325T>G		intron_variant		1
TBXA2R	ENST00000411851.3	c.722T>G	p.Val241Gly	missense_variant	2/4	2
TBXA2R	ENST00000587717.1	n.221T>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

risk factor, no assertion criteria provided

literature only

OMIM

Jul 05, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.76	T;T
M_CAP	Pathogenic	0.49	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Uncertain	-0.056	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;.
Vest4		0.54
MutPred		0.45		Gain of disorder (P = 0.0113);Gain of disorder (P = 0.0113);
MVP		0.84
MPC		1.9
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.68
gMVP		0.80

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: rs397514542; hg19: chr19-3599911;