19-3595078-TAAAAAA-TAAAAAAAA

Variant names:

• chr19-3595078-T-TAA
• rs34885751
• NM_001060.6:c.*608_*609dupTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_201636.3(TBXA2R):​c.984-4_984-3dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (70 hom., cov: 0)
  • Exomes 𝑓: 0.025 (1 hom.)
• Consequence: TBXA2R NM_201636.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94
• Publications: 3 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 19-3595078-T-TAA is Benign according to our data. Variant chr19-3595078-T-TAA is described in ClinVar as Benign. ClinVar VariationId is 1285720.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0522 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.*608_*609dupTT		3_prime_UTR	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.984-4_984-3dupTT		splice_region intron	N/A	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.*608_*609dupTT		3_prime_UTR	Exon 3 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000589966.1	TSL:1	c.*471_*472dupTT		3_prime_UTR	Exon 2 of 2	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000882306.1		c.*608_*609dupTT		3_prime_UTR	Exon 3 of 3	ENSP00000552365.1

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 3504 AN: 129448 Hom.: 70 Cov.: 0

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.0188

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.0278

Gnomad EAS AF: 0.000238

Gnomad SAS AF: 0.00358

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.0338

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0183

GnomAD2 exomes AF: 0.0264 AC: 1057 AN: 40008 AF XY: 0.0255

Gnomad AFR exome AF: 0.0585

Gnomad AMR exome AF: 0.0194

Gnomad ASJ exome AF: 0.0291

Gnomad EAS exome AF: 0.00691

Gnomad FIN exome AF: 0.0176

Gnomad NFE exome AF: 0.0334

Gnomad OTH exome AF: 0.0307

GnomAD4 exome AF: 0.0250 AC: 8608 AN: 344588 Hom.: 1 Cov.: 0 AF XY: 0.0243 AC XY: 4438 AN XY: 182982

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0458 AC: 384 AN: 8380

American (AMR) AF: 0.0162 AC: 265 AN: 16370

Ashkenazi Jewish (ASJ) AF: 0.0336 AC: 290 AN: 8642

East Asian (EAS) AF: 0.00398 AC: 80 AN: 20076

South Asian (SAS) AF: 0.0158 AC: 654 AN: 41348

European-Finnish (FIN) AF: 0.0254 AC: 373 AN: 14702

Middle Eastern (MID) AF: 0.0285 AC: 34 AN: 1192

European-Non Finnish (NFE) AF: 0.0280 AC: 6069 AN: 216830

Other (OTH) AF: 0.0269 AC: 459 AN: 17048

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0271 AC: 3505 AN: 129458 Hom.: 70 Cov.: 0 AF XY: 0.0264 AC XY: 1626 AN XY: 61590

African (AFR) AF: 0.0543 AC: 1854 AN: 34170

American (AMR) AF: 0.0148 AC: 187 AN: 12652

Ashkenazi Jewish (ASJ) AF: 0.0278 AC: 90 AN: 3242

East Asian (EAS) AF: 0.000238 AC: 1 AN: 4196

South Asian (SAS) AF: 0.00359 AC: 14 AN: 3896

European-Finnish (FIN) AF: 0.0121 AC: 81 AN: 6702

Middle Eastern (MID) AF: 0.0325 AC: 8 AN: 246

European-Non Finnish (NFE) AF: 0.0198 AC: 1223 AN: 61802

Other (OTH) AF: 0.0182 AC: 32 AN: 1754

Alfa AF: 0.00401 Hom.: 409

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34885751; hg19: chr19-3595076;