19-3595698-CCGGAGCG-C

Position:

• chr19-3595698-CCGGAGCG-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001060.6(TBXA2R):​c.1015_1021del​(p.Arg339GlyfsTer29) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TBXA2R NM_001060.6 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.469

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXA2R	NM_001060.6	c.1015_1021del	p.Arg339GlyfsTer29	frameshift_variant	3/3	ENST00000375190.10	NP_001051.1
TBXA2R	XM_011528214.3	c.1015_1021del	p.Arg339GlyfsTer29	frameshift_variant	4/4		XP_011526516.1
TBXA2R	NM_201636.3	c.983+32_983+38del		intron_variant			NP_963998.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXA2R	ENST00000375190.10	c.1015_1021del	p.Arg339GlyfsTer29	frameshift_variant	3/3	1	NM_001060.6	ENSP00000364336	P1
TBXA2R	ENST00000589966.1	c.626_632del	p.Ala209GlyfsTer4	frameshift_variant	2/2	1		ENSP00000468145
TBXA2R	ENST00000411851.3	c.983+32_983+38del		intron_variant		2		ENSP00000393333

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 04, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with TBXA2R-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the TBXA2R gene (p.Arg339Glyfs*29). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 5 amino acid(s) of the TBXA2R protein and extend the protein by 23 additional amino acid residues. -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr19-3595696;