rs5748

chr19-3600200-C-Achr19-3600200-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001060.6(TBXA2R):c.435G>T(p.Ser145=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 1,597,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S145S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: TBXA2R NM_001060.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.837

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 19-3600200-C-A is Benign according to our data. Variant chr19-3600200-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2053452.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.837 with no splicing effect.
• BS2: High AC in GnomAd at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBXA2R	NM_001060.6	c.435G>T	p.Ser145=	synonymous_variant	2/3	ENST00000375190.10
TBXA2R	NM_201636.3	c.435G>T	p.Ser145=	synonymous_variant	2/4
TBXA2R	XM_011528214.3	c.435G>T	p.Ser145=	synonymous_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXA2R	ENST00000375190.10	c.435G>T	p.Ser145=	synonymous_variant	2/3	1	NM_001060.6	P1
TBXA2R	ENST00000589966.1	c.397+38G>T		intron_variant		1
TBXA2R	ENST00000411851.3	c.435G>T	p.Ser145=	synonymous_variant	2/4	2

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 151972 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000408 AC: 86 AN: 210950 Hom.: 0 AF XY: 0.000427 AC XY: 50 AN XY: 117150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000346

Gnomad FIN exome AF: 0.000169

Gnomad NFE exome AF: 0.000904

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000447 AC: 646 AN: 1446022 Hom.: 0 Cov.: 32 AF XY: 0.000447 AC XY: 321 AN XY: 718402

Gnomad4 AFR exome AF: 0.000121

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.000142

Gnomad4 NFE exome AF: 0.000545

Gnomad4 OTH exome AF: 0.000519

GnomAD4 genome AF: 0.000197 AC: 30 AN: 151972 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74238

Gnomad4 AFR AF: 0.0000966

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.000479

Alfa AF: 0.000107 Hom.: 36

Bravo AF: 0.000215

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

Invitae

Nov 14, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	0.15
Dann	Benign	0.92

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: rs5748; hg19: chr19-3600198;