19-3600456-C-T

Variant names:

• chr19-3600456-C-T
• rs34377097
• NM_001060.6:c.179G>A

Variant summary

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

The NM_001060.6(TBXA2R):​c.179G>A​(p.Arg60His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R60L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBXA2R NM_001060.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 25 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):

• 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: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXA2R	NM_001060.6	c.179G>A	p.Arg60His	missense_variant	Exon 2 of 3	ENST00000375190.10	NP_001051.1
TBXA2R	NM_201636.3	c.179G>A	p.Arg60His	missense_variant	Exon 2 of 4		NP_963998.2
TBXA2R	XM_011528214.3	c.179G>A	p.Arg60His	missense_variant	Exon 3 of 4		XP_011526516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXA2R	ENST00000375190.10	c.179G>A	p.Arg60His	missense_variant	Exon 2 of 3	1	NM_001060.6	ENSP00000364336.4
TBXA2R	ENST00000589966.1	c.179G>A	p.Arg60His	missense_variant	Exon 1 of 2	1		ENSP00000468145.1
TBXA2R	ENST00000411851.3	c.179G>A	p.Arg60His	missense_variant	Exon 2 of 4	2		ENSP00000393333.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.64	D;.;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.018
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Uncertain	0.096	D
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.6	M;.;M
PhyloP100		1.1
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.6	D;.;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0050	D;.;D
Sift4G	Uncertain	0.037	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.47
MutPred		0.75		Loss of methylation at R60 (P = 0.0358);Loss of methylation at R60 (P = 0.0358);Loss of methylation at R60 (P = 0.0358);
MVP		0.67
MPC		1.9
ClinPred		0.99	D
GERP RS		4.6
PromoterAI		0.032	Neutral
Varity_R		0.38
gMVP		0.64
Mutation Taster		=45/55	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

Other links and lift over

dbSNP: rs34377097; hg19: chr19-3600454; COSMIC: COSV64343616; COSMIC: COSV64343616;