Variant rs1056048 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001366285.2(TBXT):c.363C>T(p.Ser121=) variant causes a synonymous change. The variant allele was found at a frequency of 0.212 in 1,613,756 control chromosomes in the GnomAD database, including 38,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 5169 hom., cov: 33)

Exomes 𝑓: 0.21 ( 33268 hom. )

Consequence

TBXT
NM_001366285.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.79

Variant links:

Genes affected

TBXT (HGNC:11515): (T-box transcription factor T) The protein encoded by this gene is an embryonic nuclear transcription factor that binds to a specific DNA element, the palindromic T-site. It binds through a region in its N-terminus, called the T-box, and effects transcription of genes required for mesoderm formation and differentiation. The protein is localized to notochord-derived cells. Variation in this gene was associated with susceptibility to neural tube defects and chordoma. A mutation in this gene was found in a family with sacral agenesis with vertebral anomalies. [provided by RefSeq, Sep 2018]

TBXT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 6-166166700-G-A is Benign according to our data. Variant chr6-166166700-G-A is described in ClinVar as [Benign]. Clinvar id is 1302242.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXT	NM_001366285.2 linkuse as main transcript	c.363C>T	p.Ser121=	synonymous_variant	2/8	ENST00000366876.7	NP_001353214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXT	ENST00000366876.7 linkuse as main transcript	c.363C>T	p.Ser121=	synonymous_variant	2/8	1	NM_001366285.2	ENSP00000355841	P4
TBXT	ENST00000366871.7 linkuse as main transcript	c.363C>T	p.Ser121=	synonymous_variant	3/8	1		ENSP00000355836		O15178-2
TBXT	ENST00000296946.6 linkuse as main transcript	c.363C>T	p.Ser121=	synonymous_variant	3/9	5		ENSP00000296946	A1	O15178-1
TBXT	ENST00000461348.2 linkuse as main transcript	c.363C>T	p.Ser121=	synonymous_variant	3/6	5		ENSP00000453512

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37469

AN:

152056

Hom.:

5152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.369

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.0419

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.257

GnomAD3 exomes

AF:

0.209

AC:

52338

AN:

250998

Hom.:

6082

AF XY:

0.204

AC XY:

27761

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.363

Gnomad AMR exome

AF:

0.235

Gnomad ASJ exome

AF:

0.259

Gnomad EAS exome

AF:

0.0328

Gnomad SAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.223

GnomAD4 exome

AF:

0.208

AC:

304206

AN:

1461582

Hom.:

33268

Cov.:

AF XY:

0.206

AC XY:

150140

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.370

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.263

Gnomad4 EAS exome

AF:

0.0340

Gnomad4 SAS exome

AF:

0.188

Gnomad4 FIN exome

AF:

0.176

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.213

GnomAD4 genome

AF:

0.247

AC:

37540

AN:

152174

Hom.:

5169

Cov.:

AF XY:

0.241

AC XY:

17906

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.369

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.266

Gnomad4 EAS

AF:

0.0422

Gnomad4 SAS

AF:

0.176

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.212

Gnomad4 OTH

AF:

0.258

Alfa

AF:

0.210

Hom.:

1680

Bravo

AF:

0.256

Asia WGS

AF:

0.163

AC:

567

AN:

3478

EpiCase

AF:

0.216

EpiControl

AF:

0.220

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 17, 2021

- -

TBXT-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.82

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