chr19-3595078-T-TAAA

Variant names:

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

Variant summary

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

The NM_201636.3(TBXA2R):​c.984-5_984-3dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 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 0.000031 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0018 (0 hom.)
• Consequence: TBXA2R NM_201636.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

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

Frequencies

GnomAD3 genomes AF: 0.0000309 AC: 4 AN: 129498 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000791

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000298

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00230 AC: 92 AN: 40008 AF XY: 0.00242

Gnomad AFR exome AF: 0.00556

Gnomad AMR exome AF: 0.00154

Gnomad ASJ exome AF: 0.00453

Gnomad EAS exome AF: 0.000545

Gnomad FIN exome AF: 0.00147

Gnomad NFE exome AF: 0.00261

Gnomad OTH exome AF: 0.00307

GnomAD4 exome AF: 0.00177 AC: 615 AN: 347316 Hom.: 0 Cov.: 0 AF XY: 0.00177 AC XY: 326 AN XY: 184456

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

African (AFR) AF: 0.00389 AC: 33 AN: 8484

American (AMR) AF: 0.00109 AC: 18 AN: 16480

Ashkenazi Jewish (ASJ) AF: 0.00263 AC: 23 AN: 8730

East Asian (EAS) AF: 0.0000496 AC: 1 AN: 20158

South Asian (SAS) AF: 0.00120 AC: 50 AN: 41690

European-Finnish (FIN) AF: 0.00176 AC: 26 AN: 14802

Middle Eastern (MID) AF: 0.000828 AC: 1 AN: 1208

European-Non Finnish (NFE) AF: 0.00198 AC: 433 AN: 218564

Other (OTH) AF: 0.00174 AC: 30 AN: 17200

⚠️ 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: 0.0000309 AC: 4 AN: 129498 Hom.: 0 Cov.: 0 AF XY: 0.0000487 AC XY: 3 AN XY: 61574

⚠️ 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: 34132

American (AMR) AF: 0.0000791 AC: 1 AN: 12648

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: 0.000298 AC: 2 AN: 6710

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

European-Non Finnish (NFE) AF: 0.0000162 AC: 1 AN: 61822

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 = 0.000000000000417111), 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		-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;