chr19-3594847-T-C

Variant names:

• chr19-3594847-T-C
• rs1011098919
• NM_001060.6:c.*841A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_201636.3(TBXA2R):​c.1213A>G​(p.Arg405Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,536,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: TBXA2R NM_201636.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0240
• 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)
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08223149).
• BS2: High AC in GnomAd4 at 6 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201636.3. 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.*841A>G		3_prime_UTR	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.1213A>G	p.Arg405Gly	missense	Exon 4 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.*841A>G		3_prime_UTR	Exon 3 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000589966.1	TSL:1	c.*704A>G		3_prime_UTR	Exon 2 of 2	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000411851.3	TSL:2	c.1213A>G	p.Arg405Gly	missense	Exon 4 of 4	ENSP00000393333.2	P21731-2

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152264 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000624 AC: 9 AN: 144146 AF XY: 0.0000519

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000366

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000939 AC: 13 AN: 1384438 Hom.: 0 Cov.: 30 AF XY: 0.00000439 AC XY: 3 AN XY: 683118

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.000364 AC: 13 AN: 35692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34750

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078690

Other (OTH) AF: 0.00 AC: 0 AN: 57886

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152382 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74520

African (AFR) AF: 0.0000481 AC: 2 AN: 41590

American (AMR) AF: 0.000261 AC: 4 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.2
DANN	Benign	0.95
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.024
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.015
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.13
MutPred		0.20		Gain of relative solvent accessibility (P = 0.0275)
MVP		0.30
MPC		1.1
ClinPred		0.035	T
GERP RS		-0.43
gMVP		0.29
Mutation Taster		=99/1	polymorphism

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: rs1011098919; hg19: chr19-3594845;