19-3595034-C-T

Variant names:

• chr19-3595034-C-T
• rs5758
• NM_001060.6:c.*654G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_201636.3(TBXA2R):​c.1026G>A​(p.Thr342Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,123,478 control chromosomes in the GnomAD database, including 142,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (15501 hom., cov: 25)
  • Exomes 𝑓: 0.50 (126612 hom.)
• Consequence: TBXA2R NM_201636.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.95
• Publications: 11 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 19-3595034-C-T is Benign according to our data. Variant chr19-3595034-C-T is described in ClinVar as Benign. ClinVar VariationId is 263264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.95 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

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.*654G>A		3_prime_UTR	Exon 3 of 3	NP_001051.1
	TBXA2R	NM_201636.3		c.1026G>A	p.Thr342Thr	synonymous	Exon 4 of 4	NP_963998.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	ENST00000375190.10	TSL:1 MANE Select	c.*654G>A		3_prime_UTR	Exon 3 of 3	ENSP00000364336.4
	TBXA2R	ENST00000589966.1	TSL:1	c.*517G>A		3_prime_UTR	Exon 2 of 2	ENSP00000468145.1
	TBXA2R	ENST00000411851.3	TSL:2	c.1026G>A	p.Thr342Thr	synonymous	Exon 4 of 4	ENSP00000393333.2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 65582 AN: 142368 Hom.: 15496 Cov.: 25

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.499

GnomAD2 exomes AF: 0.426 AC: 56865 AN: 133342 AF XY: 0.431

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.321

Gnomad ASJ exome AF: 0.539

Gnomad EAS exome AF: 0.145

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.542

Gnomad OTH exome AF: 0.477

GnomAD4 exome AF: 0.501 AC: 491742 AN: 981030 Hom.: 126612 Cov.: 13 AF XY: 0.498 AC XY: 248368 AN XY: 499166

African (AFR) AF: 0.324 AC: 7241 AN: 22360

American (AMR) AF: 0.339 AC: 11145 AN: 32870

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 11400 AN: 20794

East Asian (EAS) AF: 0.141 AC: 3889 AN: 27628

South Asian (SAS) AF: 0.370 AC: 26096 AN: 70586

European-Finnish (FIN) AF: 0.512 AC: 14739 AN: 28780

Middle Eastern (MID) AF: 0.494 AC: 1611 AN: 3264

European-Non Finnish (NFE) AF: 0.540 AC: 395097 AN: 732264

Other (OTH) AF: 0.483 AC: 20524 AN: 42484

GnomAD4 genome AF: 0.461 AC: 65601 AN: 142448 Hom.: 15501 Cov.: 25 AF XY: 0.456 AC XY: 31557 AN XY: 69276

African (AFR) AF: 0.339 AC: 12667 AN: 37322

American (AMR) AF: 0.428 AC: 6099 AN: 14238

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1892 AN: 3410

East Asian (EAS) AF: 0.160 AC: 702 AN: 4378

South Asian (SAS) AF: 0.379 AC: 1649 AN: 4354

European-Finnish (FIN) AF: 0.523 AC: 4951 AN: 9474

Middle Eastern (MID) AF: 0.581 AC: 150 AN: 258

European-Non Finnish (NFE) AF: 0.547 AC: 36218 AN: 66188

Other (OTH) AF: 0.498 AC: 984 AN: 1974

Alfa AF: 0.495 Hom.: 3419

Bravo AF: 0.427

Asia WGS AF: 0.289 AC: 1008 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.76
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs5758; hg19: chr19-3595032; COSMIC: COSV59258203; COSMIC: COSV59258203;