19-3595078-TAAAAAA-TAAAAAAA

Variant names:

• chr19-3595078-T-TA
• rs34885751
• NM_001060.6:c.*609dupT

Variant summary

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

The NM_201636.3(TBXA2R):​c.984-3dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (11618 hom., cov: 0)
  • Exomes 𝑓: 0.23 (111 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-TA is Benign according to our data. Variant chr19-3595078-T-TA is described in ClinVar as Benign. ClinVar VariationId is 1240852.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 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.*609dupT		3_prime_UTR	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.984-3dupT		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.*609dupT		3_prime_UTR	Exon 3 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000589966.1	TSL:1	c.*472dupT		3_prime_UTR	Exon 2 of 2	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000882306.1		c.*609dupT		3_prime_UTR	Exon 3 of 3	ENSP00000552365.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 54650 AN: 129266 Hom.: 11618 Cov.: 0

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.0740

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.446

GnomAD2 exomes AF: 0.214 AC: 8545 AN: 40008 AF XY: 0.215

Gnomad AFR exome AF: 0.304

Gnomad AMR exome AF: 0.175

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.0804

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.274

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.227 AC: 78213 AN: 344546 Hom.: 111 Cov.: 0 AF XY: 0.223 AC XY: 40867 AN XY: 182998

African (AFR) AF: 0.269 AC: 2255 AN: 8392

American (AMR) AF: 0.165 AC: 2676 AN: 16250

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 2049 AN: 8662

East Asian (EAS) AF: 0.0741 AC: 1488 AN: 20070

South Asian (SAS) AF: 0.172 AC: 7086 AN: 41184

European-Finnish (FIN) AF: 0.241 AC: 3550 AN: 14734

Middle Eastern (MID) AF: 0.235 AC: 281 AN: 1196

European-Non Finnish (NFE) AF: 0.253 AC: 54871 AN: 216992

Other (OTH) AF: 0.232 AC: 3957 AN: 17066

GnomAD4 genome AF: 0.423 AC: 54652 AN: 129276 Hom.: 11618 Cov.: 0 AF XY: 0.415 AC XY: 25546 AN XY: 61514

African (AFR) AF: 0.465 AC: 15859 AN: 34134

American (AMR) AF: 0.332 AC: 4199 AN: 12638

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1448 AN: 3236

East Asian (EAS) AF: 0.0743 AC: 311 AN: 4188

South Asian (SAS) AF: 0.251 AC: 974 AN: 3888

European-Finnish (FIN) AF: 0.414 AC: 2785 AN: 6720

Middle Eastern (MID) AF: 0.421 AC: 102 AN: 242

European-Non Finnish (NFE) AF: 0.453 AC: 27934 AN: 61682

Other (OTH) AF: 0.447 AC: 782 AN: 1750

Alfa AF: 0.155 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 (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: rs34885751; hg19: chr19-3595076;