19-3600200-C-A

Variant names:

• chr19-3600200-C-A
• rs5748
• NM_001060.6:c.435G>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001060.6(TBXA2R):​c.435G>T​(p.Ser145Ser) 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
• Publications: 15 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 -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 VariationId 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 GnomAd4 at 30 Unknown,AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	NM_001060.6	MANE Select	c.435G>T	p.Ser145Ser	synonymous	Exon 2 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.435G>T	p.Ser145Ser	synonymous	Exon 2 of 4	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.435G>T	p.Ser145Ser	synonymous	Exon 2 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000589966.1	TSL:1	c.397+38G>T		intron	N/A	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000411851.3	TSL:2	c.435G>T	p.Ser145Ser	synonymous	Exon 2 of 4	ENSP00000393333.2	P21731-2

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

GnomAD2 exomes AF: 0.000408 AC: 86 AN: 210950 AF XY: 0.000427

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 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

African (AFR) AF: 0.000121 AC: 4 AN: 33160

American (AMR) AF: 0.00 AC: 0 AN: 42654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25842

East Asian (EAS) AF: 0.00 AC: 0 AN: 38984

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85206

European-Finnish (FIN) AF: 0.000142 AC: 7 AN: 49386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.000545 AC: 603 AN: 1105444

Other (OTH) AF: 0.000519 AC: 31 AN: 59694

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

African (AFR) AF: 0.0000966 AC: 4 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 67970

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.000107 Hom.: 36

Bravo AF: 0.000215

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.15
DANN	Benign	0.92
PhyloP100		0.84
PromoterAI		-0.014	Neutral

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: rs5748; hg19: chr19-3600198;