chr19-3595034-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001060.6(TBXA2R):​c.*654G>C variant causes a 3 prime UTR 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_001060.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 11 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):

• qualitative platelet defect

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• bleeding diathesis due to thromboxane synthesis deficiency

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001060.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	NM_001060.6	MANE Select	c.*654G>C		3_prime_UTR	Exon 3 of 3	NP_001051.1
	TBXA2R	NM_201636.3		c.1026G>C	p.Thr342Thr	synonymous	Exon 4 of 4	NP_963998.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	ENST00000375190.10	TSL:1 MANE Select	c.*654G>C		3_prime_UTR	Exon 3 of 3	ENSP00000364336.4
	TBXA2R	ENST00000589966.1	TSL:1	c.*517G>C		3_prime_UTR	Exon 2 of 2	ENSP00000468145.1
	TBXA2R	ENST00000411851.3	TSL:2	c.1026G>C	p.Thr342Thr	synonymous	Exon 4 of 4	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

African (AFR) AF: 0.00 AC: 0 AN: 22450

American (AMR) AF: 0.00 AC: 0 AN: 32998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20860

East Asian (EAS) AF: 0.00 AC: 0 AN: 27746

South Asian (SAS) AF: 0.00 AC: 0 AN: 70726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3268

European-Non Finnish (NFE) AF: 0.00000136 AC: 1 AN: 735060

Other (OTH) AF: 0.00 AC: 0 AN: 42652

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 3419

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.28
PhyloP100		-2.0

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: rs5758; hg19: chr19-3595032;