19-3595078-TAA-T

Variant names:

• chr19-3595078-TAA-T
• rs34885751
• NM_001060.6:c.*608_*609delTT

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.984-4_984-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 468,042 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. 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_201636.3 splice_region, intron
• 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

Our verdict: Benign. The variant received -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. GnomAdExome4 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 GnomAdExome4. There are 5871 alleles in the male GnomAdExome4 subpopulation. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXA2R	NM_001060.6	c.*608_*609delTT		3_prime_UTR_variant	Exon 3 of 3	ENST00000375190.10	NP_001051.1
TBXA2R	XM_011528214.3	c.*608_*609delTT		3_prime_UTR_variant	Exon 4 of 4		XP_011526516.1
TBXA2R	NM_201636.3	c.984-4_984-3delTT		splice_region_variant, intron_variant	Intron 3 of 3		NP_963998.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXA2R	ENST00000375190	c.*608_*609delTT		3_prime_UTR_variant	Exon 3 of 3	1	NM_001060.6	ENSP00000364336.4
TBXA2R	ENST00000589966	c.*471_*472delTT		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000468145.1
TBXA2R	ENST00000411851.3	c.984-4_984-3delTT		splice_region_variant, intron_variant	Intron 3 of 3	2		ENSP00000393333.2

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

GnomAD2 exomes AF: 0.0376 AC: 1505 AN: 40008 AF XY: 0.0375

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 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 AC: 252 AN: 8334

Gnomad4 AMR exome AF: 0.0378 AC: 602 AN: 15930

Gnomad4 ASJ exome AF: 0.0371 AC: 316 AN: 8524

Gnomad4 EAS exome AF: 0.0496 AC: 957 AN: 19298

Gnomad4 SAS exome AF: 0.0375 AC: 1510 AN: 40218

Gnomad4 FIN exome AF: 0.0311 AC: 450 AN: 14472

Gnomad4 NFE exome AF: 0.0285 AC: 6102 AN: 213894

Gnomad4 Remaining exome AF: 0.0345 AC: 579 AN: 16764

⚠️ The allele balance in gnomAD4 Exomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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 AC: 0.0000879147 AN: 0.0000879147

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.000308 AC: 0.000308452 AN: 0.000308452

Gnomad4 EAS AF: 0.000238 AC: 0.000237643 AN: 0.000237643

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.000598 AC: 0.00059755 AN: 0.00059755

Gnomad4 NFE AF: 0.0000485 AC: 0.0000485437 AN: 0.0000485437

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Genomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 409

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 05, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=100/0	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

Publications

LitVar

Other links and lift over

dbSNP: rs34885751; hg19: chr19-3595076;