19-3595034-C-G

Variant names:

• chr19-3595034-C-G
• rs5758
• NM_001060.6:c.*654G>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_201636.3(TBXA2R):​c.1026G>C​(p.Thr342Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 984,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 25)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: TBXA2R NM_201636.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP7: Synonymous conserved (PhyloP=-1.95 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXA2R	NM_001060.6	c.*654G>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000375190.10	NP_001051.1
TBXA2R	NM_201636.3	c.1026G>C	p.Thr342Thr	synonymous_variant	Exon 4 of 4		NP_963998.2
TBXA2R	XM_011528214.3	c.*654G>C		3_prime_UTR_variant	Exon 4 of 4		XP_011526516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXA2R	ENST00000375190	c.*654G>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_001060.6	ENSP00000364336.4
TBXA2R	ENST00000589966	c.*517G>C		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000468145.1
TBXA2R	ENST00000411851.3	c.1026G>C	p.Thr342Thr	synonymous_variant	Exon 4 of 4	2		ENSP00000393333.2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 984626 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 500934

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: 0.00000136

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.28

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: rs5758; hg19: chr19-3595032;