19-3595699-C-G

Variant names:

• chr19-3595699-C-G
• NM_001060.6:c.1021G>C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001060.6(TBXA2R):​c.1021G>C​(p.Gly341Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000488 in 1,435,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: TBXA2R NM_001060.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.053248614).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXA2R	NM_001060.6	c.1021G>C	p.Gly341Arg	missense_variant	Exon 3 of 3	ENST00000375190.10	NP_001051.1
TBXA2R	XM_011528214.3	c.1021G>C	p.Gly341Arg	missense_variant	Exon 4 of 4		XP_011526516.1
TBXA2R	NM_201636.3	c.983+38G>C		intron_variant	Intron 3 of 3		NP_963998.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXA2R	ENST00000375190.10	c.1021G>C	p.Gly341Arg	missense_variant	Exon 3 of 3	1	NM_001060.6	ENSP00000364336.4
TBXA2R	ENST00000589966.1	c.632G>C	p.Arg211Pro	missense_variant	Exon 2 of 2	1		ENSP00000468145.1
TBXA2R	ENST00000411851.3	c.983+38G>C		intron_variant	Intron 3 of 3	2		ENSP00000393333.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000488 AC: 7 AN: 1435758 Hom.: 0 Cov.: 69 AF XY: 0.00000703 AC XY: 5 AN XY: 711536

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000636

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.070
DANN	Benign	0.72
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PROVEAN	Benign	0.41	N
REVEL	Benign	0.040
Sift	Benign	0.81	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.039
MutPred		0.17		Gain of solvent accessibility (P = 0.0037);
MVP		0.18
ClinPred		0.024	T
GERP RS		-7.2
Varity_R		0.030

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-3595697;