chr19-3595413-T-C

Variant names:

• chr19-3595413-T-C
• rs5754
• NM_001060.6:c.*275A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001060.6(TBXA2R):​c.*275A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,392,400 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0084 (18 hom., cov: 33)
  • Exomes 𝑓: 0.00077 (9 hom.)
• Consequence: TBXA2R NM_001060.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.726
• Publications: 4 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):

• bleeding diathesis due to thromboxane synthesis deficiency

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

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• schizophrenia

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 19-3595413-T-C is Benign according to our data. Variant chr19-3595413-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1218080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00836 (1266/151366) while in subpopulation AFR AF = 0.0284 (1175/41352). AF 95% confidence interval is 0.0271. There are 18 homozygotes in GnomAd4. There are 617 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1266 Unknown,AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	NM_001060.6	MANE Select	c.*275A>G		3_prime_UTR	Exon 3 of 3	NP_001051.1	P21731-3
	TBXA2R	NM_201636.3		c.983+324A>G		intron	N/A	NP_963998.2	P21731-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXA2R	ENST00000375190.10	TSL:1 MANE Select	c.*275A>G		3_prime_UTR	Exon 3 of 3	ENSP00000364336.4	P21731-3
	TBXA2R	ENST00000589966.1	TSL:1	c.*138A>G		3_prime_UTR	Exon 2 of 2	ENSP00000468145.1	K7ER80
	TBXA2R	ENST00000882306.1		c.*275A>G		3_prime_UTR	Exon 3 of 3	ENSP00000552365.1

Frequencies

GnomAD3 genomes AF: 0.00817 AC: 1236 AN: 151276 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00316

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00771

GnomAD4 exome AF: 0.000765 AC: 950 AN: 1241034 Hom.: 9 Cov.: 40 AF XY: 0.000711 AC XY: 424 AN XY: 596412

African (AFR) AF: 0.0247 AC: 684 AN: 27718

American (AMR) AF: 0.00260 AC: 45 AN: 17276

Ashkenazi Jewish (ASJ) AF: 0.00194 AC: 35 AN: 18064

East Asian (EAS) AF: 0.00 AC: 0 AN: 33756

South Asian (SAS) AF: 0.000142 AC: 7 AN: 49344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28890

Middle Eastern (MID) AF: 0.00143 AC: 5 AN: 3494

European-Non Finnish (NFE) AF: 0.0000594 AC: 60 AN: 1010836

Other (OTH) AF: 0.00221 AC: 114 AN: 51656

GnomAD4 genome AF: 0.00836 AC: 1266 AN: 151366 Hom.: 18 Cov.: 33 AF XY: 0.00835 AC XY: 617 AN XY: 73920

African (AFR) AF: 0.0284 AC: 1175 AN: 41352

American (AMR) AF: 0.00315 AC: 48 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10256

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67822

Other (OTH) AF: 0.00763 AC: 16 AN: 2098

Alfa AF: 0.00548 Hom.: 2

Bravo AF: 0.00878

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.44
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism

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: rs5754; hg19: chr19-3595411;