19-3595078-TAAAAAA-TAAA

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_201636.3(TBXA2R):​c.984-5_984-3delTTT variant causes a splice region, intron 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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_201636.3 splice_region, intron
• 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_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_*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;