19-3595078-TAA-T

Position:

• chr19-3595078-TAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001060.6(TBXA2R):​c.*608_*609del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 468,042 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000093 (0 hom., cov: 0)
  • Exomes 𝑓: 0.032 (0 hom.)
• Consequence: TBXA2R NM_001060.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.623

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-3595078-TAA-T is Benign according to our data. Variant chr19-3595078-TAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1207313.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0319 (10806/338606) while in subpopulation EAS AF= 0.0496 (957/19298). AF 95% confidence interval is 0.047. There are 0 homozygotes in gnomad4_exome. There are 5871 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXA2R	NM_001060.6	c.*608_*609del		3_prime_UTR_variant	3/3	ENST00000375190.10	NP_001051.1
TBXA2R	XM_011528214.3	c.*608_*609del		3_prime_UTR_variant	4/4		XP_011526516.1
TBXA2R	NM_201636.3	c.984-4_984-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_963998.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXA2R	ENST00000375190.10	c.*608_*609del		3_prime_UTR_variant	3/3	1	NM_001060.6	ENSP00000364336	P1
TBXA2R	ENST00000589966.1	c.*471_*472del		3_prime_UTR_variant	2/2	1		ENSP00000468145
TBXA2R	ENST00000411851.3	c.984-4_984-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000393333

Frequencies

GnomAD3 genomes AF: 0.0000927 AC: 12 AN: 129436 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000879

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000308

Gnomad EAS AF: 0.000238

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000598

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000485

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0376 AC: 1505 AN: 40008 Hom.: 0 AF XY: 0.0375 AC XY: 761 AN XY: 20288

Gnomad AFR exome AF: 0.0269

Gnomad AMR exome AF: 0.0386

Gnomad ASJ exome AF: 0.0323

Gnomad EAS exome AF: 0.0467

Gnomad SAS exome AF: 0.0489

Gnomad FIN exome AF: 0.0485

Gnomad NFE exome AF: 0.0325

Gnomad OTH exome AF: 0.0391

GnomAD4 exome AF: 0.0319 AC: 10806 AN: 338606 Hom.: 0 AF XY: 0.0327 AC XY: 5871 AN XY: 179810

Gnomad4 AFR exome AF: 0.0302

Gnomad4 AMR exome AF: 0.0378

Gnomad4 ASJ exome AF: 0.0371

Gnomad4 EAS exome AF: 0.0496

Gnomad4 SAS exome AF: 0.0375

Gnomad4 FIN exome AF: 0.0311

Gnomad4 NFE exome AF: 0.0285

Gnomad4 OTH exome AF: 0.0345

GnomAD4 genome AF: 0.0000927 AC: 12 AN: 129436 Hom.: 0 Cov.: 0 AF XY: 0.000130 AC XY: 8 AN XY: 61538

Gnomad4 AFR AF: 0.0000879

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000308

Gnomad4 EAS AF: 0.000238

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000598

Gnomad4 NFE AF: 0.0000485

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs34885751; hg19: chr19-3595076;