19-3595078-TA-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_201636.3(TBXA2R):​c.984-3delT 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 0.0088 (7 hom., cov: 0)
  • Exomes 𝑓: 0.21 (0 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-TA-T is Benign according to our data. Variant chr19-3595078-TA-T is described in ClinVar as Benign. ClinVar VariationId is 1239007.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00877 (1135/129442) while in subpopulation AFR AF = 0.0248 (847/34178). AF 95% confidence interval is 0.0234. There are 7 homozygotes in GnomAd4. There are 531 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1135 Unknown,AD gene.

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.*609delT		3_prime_UTR	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.984-3delT		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.*609delT		3_prime_UTR	Exon 3 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000589966.1	TSL:1	c.*472delT		3_prime_UTR	Exon 2 of 2	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000882306.1		c.*609delT		3_prime_UTR	Exon 3 of 3	ENSP00000552365.1

Frequencies

GnomAD3 genomes AF: 0.00873 AC: 1130 AN: 129432 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00704

Gnomad ASJ AF: 0.00216

Gnomad EAS AF: 0.00190

Gnomad SAS AF: 0.00102

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00149

Gnomad OTH AF: 0.00742

GnomAD2 exomes AF: 0.277 AC: 11065 AN: 40008 AF XY: 0.276

Gnomad AFR exome AF: 0.203

Gnomad AMR exome AF: 0.312

Gnomad ASJ exome AF: 0.232

Gnomad EAS exome AF: 0.386

Gnomad FIN exome AF: 0.284

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.210 AC: 71111 AN: 339270 Hom.: 0 Cov.: 0 AF XY: 0.213 AC XY: 38317 AN XY: 179904

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

African (AFR) AF: 0.186 AC: 1542 AN: 8310

American (AMR) AF: 0.264 AC: 4179 AN: 15818

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 1697 AN: 8546

East Asian (EAS) AF: 0.319 AC: 6233 AN: 19568

South Asian (SAS) AF: 0.259 AC: 10356 AN: 39910

European-Finnish (FIN) AF: 0.202 AC: 2927 AN: 14496

Middle Eastern (MID) AF: 0.195 AC: 231 AN: 1186

European-Non Finnish (NFE) AF: 0.189 AC: 40484 AN: 214568

Other (OTH) AF: 0.205 AC: 3462 AN: 16868

⚠️ 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: 0.00877 AC: 1135 AN: 129442 Hom.: 7 Cov.: 0 AF XY: 0.00862 AC XY: 531 AN XY: 61574

African (AFR) AF: 0.0248 AC: 847 AN: 34178

American (AMR) AF: 0.00720 AC: 91 AN: 12646

Ashkenazi Jewish (ASJ) AF: 0.00216 AC: 7 AN: 3242

East Asian (EAS) AF: 0.00191 AC: 8 AN: 4194

South Asian (SAS) AF: 0.000770 AC: 3 AN: 3896

European-Finnish (FIN) AF: 0.0111 AC: 74 AN: 6696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 246

European-Non Finnish (NFE) AF: 0.00149 AC: 92 AN: 61790

Other (OTH) AF: 0.00740 AC: 13 AN: 1756

Alfa AF: 0.00 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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs34885751; hg19: chr19-3595076;