NM_001060.6:c.*608_*609delTT

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001060.6(TBXA2R):​c.*608_*609delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 468,042 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000093 (0 hom., cov: 0)
  • Exomes 𝑓: 0.032 (0 hom.)
• Consequence: TBXA2R NM_001060.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.623
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 19-3595078-TAA-T is Benign according to our data. Variant chr19-3595078-TAA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1207313.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001060.6. 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_*609delTT		3_prime_UTR	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.984-4_984-3delTT		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_*609delTT		3_prime_UTR	Exon 3 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000589966.1	TSL:1	c.*471_*472delTT		3_prime_UTR	Exon 2 of 2	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000882306.1		c.*608_*609delTT		3_prime_UTR	Exon 3 of 3	ENSP00000552365.1

Frequencies

GnomAD3 genomes AF: 0.0000927 AC: 12 AN: 129436 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000879

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000308

Gnomad EAS AF: 0.000238

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000598

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000485

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0376 AC: 1505 AN: 40008 AF XY: 0.0375

Gnomad AFR exome AF: 0.0269

Gnomad AMR exome AF: 0.0386

Gnomad ASJ exome AF: 0.0323

Gnomad EAS exome AF: 0.0467

Gnomad FIN exome AF: 0.0485

Gnomad NFE exome AF: 0.0325

Gnomad OTH exome AF: 0.0391

GnomAD4 exome AF: 0.0319 AC: 10806 AN: 338606 Hom.: 0 AF XY: 0.0327 AC XY: 5871 AN XY: 179810

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

African (AFR) AF: 0.0302 AC: 252 AN: 8334

American (AMR) AF: 0.0378 AC: 602 AN: 15930

Ashkenazi Jewish (ASJ) AF: 0.0371 AC: 316 AN: 8524

East Asian (EAS) AF: 0.0496 AC: 957 AN: 19298

South Asian (SAS) AF: 0.0375 AC: 1510 AN: 40218

European-Finnish (FIN) AF: 0.0311 AC: 450 AN: 14472

Middle Eastern (MID) AF: 0.0324 AC: 38 AN: 1172

European-Non Finnish (NFE) AF: 0.0285 AC: 6102 AN: 213894

Other (OTH) AF: 0.0345 AC: 579 AN: 16764

⚠️ 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: 0.0000927 AC: 12 AN: 129436 Hom.: 0 Cov.: 0 AF XY: 0.000130 AC XY: 8 AN XY: 61538

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

African (AFR) AF: 0.0000879 AC: 3 AN: 34124

American (AMR) AF: 0.00 AC: 0 AN: 12634

Ashkenazi Jewish (ASJ) AF: 0.000308 AC: 1 AN: 3242

East Asian (EAS) AF: 0.000238 AC: 1 AN: 4208

South Asian (SAS) AF: 0.00 AC: 0 AN: 3918

European-Finnish (FIN) AF: 0.000598 AC: 4 AN: 6694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.0000485 AC: 3 AN: 61800

Other (OTH) AF: 0.00 AC: 0 AN: 1752

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 409

ClinVar

ClinVar submissions

Significance: Likely 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		-0.62
Mutation Taster		=100/0	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: rs34885751; hg19: chr19-3595076;