Variant chr19-47802309-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001397346.1(TPRX1):c.867G>A(p.Pro289Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,210,498 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 1 hom., cov: 24)

Exomes 𝑓: 0.0046 ( 145 hom. )

Consequence

TPRX1
NM_001397346.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.09

Variant links:

Genes affected

TPRX1 (HGNC:32174): (tetrapeptide repeat homeobox 1) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the TPRX homeobox gene family. [provided by RefSeq, Jul 2008]

TPRX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 19-47802309-C-T is Benign according to our data. Variant chr19-47802309-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650192.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.09 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 145 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPRX1	NM_001397346.1 linkuse as main transcript	c.867G>A	p.Pro289Pro	synonymous_variant	3/3	ENST00000698655.1	NP_001384275.1
TPRX1	NM_198479.3 linkuse as main transcript	c.993G>A	p.Pro331Pro	synonymous_variant	4/4		NP_940881.3	Q8N7U7D2CFI5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TPRX1	ENST00000698655.1 linkuse as main transcript	c.867G>A	p.Pro289Pro	synonymous_variant	3/3		NM_001397346.1	ENSP00000513863.1	A0A8V8TMK4
TPRX1	ENST00000535759.2 linkuse as main transcript	c.993G>A	p.Pro331Pro	synonymous_variant	4/4	1		ENSP00000438832.1	D2CFI5
TPRX1	ENST00000322175.8 linkuse as main transcript	c.605-86G>A		intron_variant		1		ENSP00000513867.1	A0A8V8TM49

Frequencies

GnomAD3 genomes

AF:

0.00426

AC:

353

AN:

82780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00467

Gnomad AMR

AF:

0.000579

Gnomad ASJ

AF:

0.00742

Gnomad EAS

AF:

0.000658

Gnomad SAS

AF:

0.000387

Gnomad FIN

AF:

0.00515

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00713

Gnomad OTH

AF:

0.000911

GnomAD3 exomes

AF:

0.00251

AC:

349

AN:

139212

Hom.:

AF XY:

0.00239

AC XY:

179

AN XY:

74872

show subpopulations

Gnomad AFR exome

AF:

0.000148

Gnomad AMR exome

AF:

0.000508

Gnomad ASJ exome

AF:

0.00520

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000906

Gnomad FIN exome

AF:

0.00301

Gnomad NFE exome

AF:

0.00409

Gnomad OTH exome

AF:

0.00209

GnomAD4 exome

AF:

0.00461

AC:

5201

AN:

1127654

Hom.:

145

Cov.:

AF XY:

0.00459

AC XY:

2559

AN XY:

557118

show subpopulations

Gnomad4 AFR exome

AF:

0.000572

Gnomad4 AMR exome

AF:

0.000720

Gnomad4 ASJ exome

AF:

0.00566

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00113

Gnomad4 FIN exome

AF:

0.00403

Gnomad4 NFE exome

AF:

0.00542

Gnomad4 OTH exome

AF:

0.00272

GnomAD4 genome

AF:

0.00427

AC:

354

AN:

82844

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

158

AN XY:

40538

show subpopulations

Gnomad4 AFR

AF:

0.00121

Gnomad4 AMR

AF:

0.000579

Gnomad4 ASJ

AF:

0.00742

Gnomad4 EAS

AF:

0.000990

Gnomad4 SAS

AF:

0.000389

Gnomad4 FIN

AF:

0.00515

Gnomad4 NFE

AF:

0.00713

Gnomad4 OTH

AF:

0.000901

Alfa

AF:

0.0465

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

TPRX1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

2.5

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over