rs34486470

Variant names:

• chr19-3595008-A-G
• rs34486470
• NM_001060.6:c.*680T>C

Variant summary

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

The NM_201636.3(TBXA2R):​c.1052T>C​(p.Leu351Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,420,466 control chromosomes in the GnomAD database, including 7,354 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (910 hom., cov: 32)
  • Exomes 𝑓: 0.10 (6444 hom.)
• Consequence: TBXA2R NM_201636.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.320
• Publications: 6 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)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019531548).
• BP6: Variant 19-3595008-A-G is Benign according to our data. Variant chr19-3595008-A-G is described in ClinVar as Benign. ClinVar VariationId is 263265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201636.3. 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.*680T>C		3_prime_UTR	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.1052T>C	p.Leu351Pro	missense	Exon 4 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.*680T>C		3_prime_UTR	Exon 3 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000589966.1	TSL:1	c.*543T>C		3_prime_UTR	Exon 2 of 2	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000411851.3	TSL:2	c.1052T>C	p.Leu351Pro	missense	Exon 4 of 4	ENSP00000393333.2	P21731-2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 15830 AN: 149250 Hom.: 908 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0795

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.0667

Gnomad EAS AF: 0.0228

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.108

GnomAD2 exomes AF: 0.0840 AC: 11530 AN: 137202 AF XY: 0.0848

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.0552

Gnomad ASJ exome AF: 0.0708

Gnomad EAS exome AF: 0.0253

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.0999 AC: 127038 AN: 1271112 Hom.: 6444 Cov.: 19 AF XY: 0.0999 AC XY: 62967 AN XY: 630406

African (AFR) AF: 0.147 AC: 4164 AN: 28326

American (AMR) AF: 0.0627 AC: 2120 AN: 33804

Ashkenazi Jewish (ASJ) AF: 0.0733 AC: 1644 AN: 22414

East Asian (EAS) AF: 0.0161 AC: 504 AN: 31282

South Asian (SAS) AF: 0.0779 AC: 6025 AN: 77384

European-Finnish (FIN) AF: 0.128 AC: 3680 AN: 28734

Middle Eastern (MID) AF: 0.141 AC: 631 AN: 4480

European-Non Finnish (NFE) AF: 0.104 AC: 103164 AN: 992658

Other (OTH) AF: 0.0981 AC: 5106 AN: 52030

GnomAD4 genome AF: 0.106 AC: 15832 AN: 149354 Hom.: 910 Cov.: 32 AF XY: 0.105 AC XY: 7654 AN XY: 72804

African (AFR) AF: 0.137 AC: 5520 AN: 40290

American (AMR) AF: 0.0873 AC: 1297 AN: 14858

Ashkenazi Jewish (ASJ) AF: 0.0667 AC: 231 AN: 3462

East Asian (EAS) AF: 0.0227 AC: 115 AN: 5074

South Asian (SAS) AF: 0.0803 AC: 374 AN: 4656

European-Finnish (FIN) AF: 0.115 AC: 1169 AN: 10162

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6789 AN: 67580

Other (OTH) AF: 0.107 AC: 221 AN: 2072

Alfa AF: 0.0505 Hom.: 55

Bravo AF: 0.103

TwinsUK AF: 0.103 AC: 383

ALSPAC AF: 0.0999 AC: 385

ESP6500AA AF: 0.106 AC: 187

ESP6500EA AF: 0.0716 AC: 246

ExAC AF: 0.0776 AC: 1664

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.4
DANN	Benign	0.92
Eigen	Benign	-0.76
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.32
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.0050
Sift	Uncertain	0.025	D
Sift4G	Benign	0.29	T
Vest4		0.11
MPC		2.0
ClinPred		0.0048	T
GERP RS		0.23
gMVP		0.29
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: rs34486470; hg19: chr19-3595006;