Variant chr19-3594842-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_201636.3(TBXA2R):c.1218G>C(p.Lys406Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000717 in 1,536,376 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 1 hom. )

Consequence

TBXA2R
NM_201636.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.948

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015095055).

BP6

Variant 19-3594842-C-G is Benign according to our data. Variant chr19-3594842-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3044020.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 101 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXA2R	NM_001060.6 link	c.*846G>C		3_prime_UTR_variant	3/3	ENST00000375190.10	NP_001051.1	P21731-3Q05C92Q0VAB0
TBXA2R	NM_201636.3 link	c.1218G>C	p.Lys406Asn	missense_variant	4/4		NP_963998.2	P21731-2Q05C92Q0VAB0
TBXA2R	XM_011528214.3 link	c.*846G>C		3_prime_UTR_variant	4/4		XP_011526516.1	P21731-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBXA2R	ENST00000375190 link	c.*846G>C		3_prime_UTR_variant	3/3	1	NM_001060.6	ENSP00000364336.4	P21731-3
TBXA2R	ENST00000589966 link	c.*709G>C		3_prime_UTR_variant	2/2	1		ENSP00000468145.1	K7ER80
TBXA2R	ENST00000411851.3 link	c.1218G>C	p.Lys406Asn	missense_variant	4/4	2		ENSP00000393333.2	P21731-2

Frequencies

GnomAD3 genomes

AF:

0.000663

AC:

101

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000445

AC:

AN:

143722

Hom.:

AF XY:

0.000404

AC XY:

AN XY:

76786

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.000939

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000881

Gnomad FIN exome

AF:

0.000144

Gnomad NFE exome

AF:

0.000613

Gnomad OTH exome

AF:

0.000235

GnomAD4 exome

AF:

0.000723

AC:

1001

AN:

1384014

Hom.:

Cov.:

AF XY:

0.000734

AC XY:

501

AN XY:

682894

show subpopulations

Gnomad4 AFR exome

AF:

0.0000950

Gnomad4 AMR exome

AF:

0.000983

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000114

Gnomad4 FIN exome

AF:

0.0000576

Gnomad4 NFE exome

AF:

0.000854

Gnomad4 OTH exome

AF:

0.000501

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152362

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000646

Hom.:

Bravo

AF:

0.000695

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.000263

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TBXA2R-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 31, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.40

DANN

Benign

0.97

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.23

M_CAP

Benign

0.014

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.97

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.060

REVEL

Benign

0.0060

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.16

MutPred

0.16

Loss of ubiquitination at K406 (P = 0.0233);

MVP

0.072

MPC

1.4

ClinPred

0.042

GERP RS

-1.6

gMVP

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over