Variant 6-166165782-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001366285.2(TBXT):c.530G>A(p.Gly177Asp) variant causes a missense change. The variant allele was found at a frequency of 0.489 in 1,613,758 control chromosomes in the GnomAD database, including 196,455 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14845 hom., cov: 32)

Exomes 𝑓: 0.49 ( 181610 hom. )

Consequence

TBXT
NM_001366285.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.58

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.0517578E-4).

BP6

Variant 6-166165782-C-T is Benign according to our data. Variant chr6-166165782-C-T is described in ClinVar as [Benign]. Clinvar id is 1242832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.505 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.530G>A	p.Gly177Asp	missense_variant	3/8	ENST00000366876.7	NP_001353214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBXT	ENST00000366876.7 linkuse as main transcript	c.530G>A	p.Gly177Asp	missense_variant	3/8	1	NM_001366285.2	ENSP00000355841.3	J3KP65
TBXT	ENST00000366871.7 linkuse as main transcript	c.530G>A	p.Gly177Asp	missense_variant	4/8	1		ENSP00000355836.3	O15178-2
TBXT	ENST00000296946.6 linkuse as main transcript	c.530G>A	p.Gly177Asp	missense_variant	4/9	5		ENSP00000296946.2	O15178-1
TBXT	ENST00000461348.2 linkuse as main transcript	c.530G>A	p.Gly177Asp	missense_variant	4/6	5		ENSP00000453512.1	H0YM91

Frequencies

GnomAD3 genomes

AF:

0.428

AC:

65060

AN:

151868

Hom.:

14833

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.447

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.511

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.510

Gnomad OTH

AF:

0.477

GnomAD3 exomes

AF:

0.478

AC:

120199

AN:

251484

Hom.:

29652

AF XY:

0.483

AC XY:

65581

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.259

Gnomad AMR exome

AF:

0.541

Gnomad ASJ exome

AF:

0.553

Gnomad EAS exome

AF:

0.338

Gnomad SAS exome

AF:

0.512

Gnomad FIN exome

AF:

0.384

Gnomad NFE exome

AF:

0.513

Gnomad OTH exome

AF:

0.503

GnomAD4 exome

AF:

0.495

AC:

723283

AN:

1461772

Hom.:

181610

Cov.:

AF XY:

0.495

AC XY:

360297

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.533

Gnomad4 ASJ exome

AF:

0.561

Gnomad4 EAS exome

AF:

0.322

Gnomad4 SAS exome

AF:

0.513

Gnomad4 FIN exome

AF:

0.395

Gnomad4 NFE exome

AF:

0.509

Gnomad4 OTH exome

AF:

0.490

GnomAD4 genome

AF:

0.428

AC:

65105

AN:

151986

Hom.:

14845

Cov.:

AF XY:

0.424

AC XY:

31536

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.266

Gnomad4 AMR

AF:

0.505

Gnomad4 ASJ

AF:

0.561

Gnomad4 EAS

AF:

0.347

Gnomad4 SAS

AF:

0.513

Gnomad4 FIN

AF:

0.377

Gnomad4 NFE

AF:

0.510

Gnomad4 OTH

AF:

0.478

Alfa

AF:

0.500

Hom.:

38772

Bravo

AF:

0.431

TwinsUK

AF:

0.505

AC:

1874

ALSPAC

AF:

0.510

AC:

1965

ESP6500AA

AF:

0.264

AC:

1164

ESP6500EA

AF:

0.512

AC:

4407

ExAC

AF:

0.474

AC:

57595

Asia WGS

AF:

0.468

AC:

1627

AN:

3478

EpiCase

AF:

0.525

EpiControl

AF:

0.519

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 26, 2018

This variant is associated with the following publications: (PMID: 33536423, 23064415, 24232574, 24990759, 9202145) -

Microcephaly-thin corpus callosum-intellectual disability syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Benign

0.88

DEOGEN2

Uncertain

0.56

D;.;.;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.58

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.75

T;T;T;T

MetaRNN

Benign

0.00031

T;T;T;T

MetaSVM

Benign

-0.82

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.5

D;D;D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.021

D;T;D;T

Sift4G

Uncertain

0.053

T;D;.;T

Polyphen

0.0060

B;.;.;.

Vest4

0.24

MPC

1.4

ClinPred

0.046

GERP RS

4.1

Varity_R

0.71

gMVP

0.78

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