19-3595524-G-A

Variant names:

• chr19-3595524-G-A
• rs13306046
• NM_001060.6:c.*164C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001060.6(TBXA2R):​c.*164C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,434,332 control chromosomes in the GnomAD database, including 9,609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1197 hom., cov: 33)
  • Exomes 𝑓: 0.11 (8412 hom.)
• Consequence: TBXA2R NM_001060.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.129
• Publications: 13 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):

• qualitative platelet defect

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• bleeding diathesis due to thromboxane synthesis deficiency

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-3595524-G-A is Benign according to our data. Variant chr19-3595524-G-A is described in ClinVar as Benign. ClinVar VariationId is 1297313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	NM_001060.6	MANE Select	c.*164C>T		3_prime_UTR	Exon 3 of 3	NP_001051.1
	TBXA2R	NM_201636.3		c.983+213C>T		intron	N/A	NP_963998.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	ENST00000375190.10	TSL:1 MANE Select	c.*164C>T		3_prime_UTR	Exon 3 of 3	ENSP00000364336.4
	TBXA2R	ENST00000589966.1	TSL:1	c.*27C>T		3_prime_UTR	Exon 2 of 2	ENSP00000468145.1
	TBXA2R	ENST00000411851.3	TSL:2	c.983+213C>T		intron	N/A	ENSP00000393333.2

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17937 AN: 152130 Hom.: 1196 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0994

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.120

GnomAD2 exomes AF: 0.0972 AC: 6037 AN: 62100 AF XY: 0.0981

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.0761

Gnomad ASJ exome AF: 0.0705

Gnomad EAS exome AF: 0.0266

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.114

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.113 AC: 144349 AN: 1282084 Hom.: 8412 Cov.: 55 AF XY: 0.113 AC XY: 69971 AN XY: 620346

African (AFR) AF: 0.150 AC: 4240 AN: 28254

American (AMR) AF: 0.0800 AC: 1579 AN: 19744

Ashkenazi Jewish (ASJ) AF: 0.0725 AC: 1367 AN: 18858

East Asian (EAS) AF: 0.0146 AC: 507 AN: 34738

South Asian (SAS) AF: 0.110 AC: 6783 AN: 61938

European-Finnish (FIN) AF: 0.124 AC: 3793 AN: 30704

Middle Eastern (MID) AF: 0.145 AC: 731 AN: 5056

European-Non Finnish (NFE) AF: 0.116 AC: 119686 AN: 1029368

Other (OTH) AF: 0.106 AC: 5663 AN: 53424

GnomAD4 genome AF: 0.118 AC: 17938 AN: 152248 Hom.: 1197 Cov.: 33 AF XY: 0.116 AC XY: 8657 AN XY: 74454

African (AFR) AF: 0.146 AC: 6079 AN: 41542

American (AMR) AF: 0.0993 AC: 1518 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3470

East Asian (EAS) AF: 0.0218 AC: 113 AN: 5176

South Asian (SAS) AF: 0.107 AC: 517 AN: 4832

European-Finnish (FIN) AF: 0.122 AC: 1291 AN: 10608

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7746 AN: 68010

Other (OTH) AF: 0.118 AC: 250 AN: 2112

Alfa AF: 0.112 Hom.: 1611

Bravo AF: 0.116

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21677697)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.69
PhyloP100		0.13
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

Other links and lift over

dbSNP: rs13306046; hg19: chr19-3595522; COSMIC: COSV59258917; COSMIC: COSV59258917;