chr19-3595796-A-C

Variant names:

• chr19-3595796-A-C
• rs4523
• NM_001060.6:c.924T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001060.6(TBXA2R):​c.924T>G​(p.Tyr308*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y308Y) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TBXA2R NM_001060.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.82
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.924T>G	p.Tyr308*	stop_gained	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.924T>G	p.Tyr308*	stop_gained	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.924T>G	p.Tyr308*	stop_gained	Exon 3 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000589966.1	TSL:1	c.535T>G	p.Tyr179Asp	missense	Exon 2 of 2	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000411851.3	TSL:2	c.924T>G	p.Tyr308*	stop_gained	Exon 3 of 4	ENSP00000393333.2	P21731-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 103

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	41
DANN	Uncertain	1.0
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.31	T
PhyloP100		2.8
Sift4G	Benign	0.19	T
Vest4		0.36
MVP		0.46
GERP RS		3.1
Mutation Taster		=7/193	disease causing (fs/PTC)

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: rs4523; hg19: chr19-3595794;