19-3595710-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001060.6(TBXA2R):c.1010C>A(p.Thr337Lys) variant causes a missense 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. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T337M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TBXA2R NM_001060.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076168805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBXA2R	NM_001060.6	c.1010C>A	p.Thr337Lys	missense_variant	3/3	ENST00000375190.10
TBXA2R	XM_011528214.3	c.1010C>A	p.Thr337Lys	missense_variant	4/4
TBXA2R	NM_201636.3	c.983+27C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXA2R	ENST00000375190.10	c.1010C>A	p.Thr337Lys	missense_variant	3/3	1	NM_001060.6	P1
TBXA2R	ENST00000589966.1	c.621C>A	p.His207Gln	missense_variant	2/2	1
TBXA2R	ENST00000411851.3	c.983+27C>A		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 65

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Dec 12, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	13
Dann	Benign	0.93
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.076	T
MutationTaster	Benign	1.0	N;N;N
Sift4G	Benign	0.28	T
Vest4		0.081
MVP		0.14
ClinPred		0.080	T
GERP RS		1.1

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-3595708;