NM_001060.6:c.*607_*609delTTT

Variant names:

• chr19-3595078-TAAA-T
• rs34885751
• NM_001060.6:c.*607_*609delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001060.6(TBXA2R):​c.*607_*609delTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00304 in 474,752 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0042 (0 hom.)
• Consequence: TBXA2R NM_001060.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.*607_*609delTTT		3_prime_UTR	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.984-5_984-3delTTT		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.*607_*609delTTT		3_prime_UTR	Exon 3 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000589966.1	TSL:1	c.*470_*472delTTT		3_prime_UTR	Exon 2 of 2	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000882306.1		c.*607_*609delTTT		3_prime_UTR	Exon 3 of 3	ENSP00000552365.1

Frequencies

GnomAD3 genomes AF: 0.0000154 AC: 2 AN: 129476 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000149

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00467 AC: 187 AN: 40008 AF XY: 0.00419

Gnomad AFR exome AF: 0.00381

Gnomad AMR exome AF: 0.00538

Gnomad ASJ exome AF: 0.00776

Gnomad EAS exome AF: 0.00364

Gnomad FIN exome AF: 0.00735

Gnomad NFE exome AF: 0.00353

Gnomad OTH exome AF: 0.00307

GnomAD4 exome AF: 0.00418 AC: 1443 AN: 345276 Hom.: 0 AF XY: 0.00403 AC XY: 739 AN XY: 183294

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

African (AFR) AF: 0.00426 AC: 36 AN: 8444

American (AMR) AF: 0.00502 AC: 82 AN: 16330

Ashkenazi Jewish (ASJ) AF: 0.00600 AC: 52 AN: 8668

East Asian (EAS) AF: 0.00536 AC: 107 AN: 19952

South Asian (SAS) AF: 0.00361 AC: 149 AN: 41246

European-Finnish (FIN) AF: 0.00476 AC: 70 AN: 14714

Middle Eastern (MID) AF: 0.00252 AC: 3 AN: 1190

European-Non Finnish (NFE) AF: 0.00403 AC: 876 AN: 217610

Other (OTH) AF: 0.00397 AC: 68 AN: 17122

⚠️ 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: 0.0000154 AC: 2 AN: 129476 Hom.: 0 Cov.: 0 AF XY: 0.0000162 AC XY: 1 AN XY: 61562

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

African (AFR) AF: 0.00 AC: 0 AN: 34130

American (AMR) AF: 0.00 AC: 0 AN: 12644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3242

East Asian (EAS) AF: 0.00 AC: 0 AN: 4210

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

European-Finnish (FIN) AF: 0.000149 AC: 1 AN: 6700

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

European-Non Finnish (NFE) AF: 0.0000162 AC: 1 AN: 61818

Other (OTH) AF: 0.00 AC: 0 AN: 1750

⚠️ 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.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.32
Mutation Taster		=86/14	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;