Genetic Variant NM_001366285.2:c.1179G>A (chr6-166158447-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001366285.2(TBXT):c.1179G>A(p.Ala393Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,613,956 control chromosomes in the GnomAD database, including 69,320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.23 ( 4910 hom., cov: 33)

Exomes 𝑓: 0.29 ( 64410 hom. )

Consequence

TBXT
NM_001366285.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.99

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 6-166158447-C-T is Benign according to our data. Variant chr6-166158447-C-T is described in ClinVar as [Benign]. Clinvar id is 1241738.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.99 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXT	NM_001366285.2 link	c.1179G>A	p.Ala393Ala	synonymous_variant	Exon 8 of 8	ENST00000366876.7	NP_001353214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TBXT	ENST00000366876.7 link	c.1179G>A	p.Ala393Ala	synonymous_variant	Exon 8 of 8	1	NM_001366285.2	ENSP00000355841.3	J3KP65
TBXT	ENST00000366871.7 link	c.1002G>A	p.Ala334Ala	synonymous_variant	Exon 8 of 8	1		ENSP00000355836.3	O15178-2
TBXT	ENST00000296946.6 link	c.1176G>A	p.Ala392Ala	synonymous_variant	Exon 9 of 9	5		ENSP00000296946.2	O15178-1

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35320

AN:

152072

Hom.:

4908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0786

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.258

GnomAD3 exomes

AF:

0.281

AC:

70599

AN:

251018

Hom.:

10347

AF XY:

0.286

AC XY:

38785

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.0745

Gnomad AMR exome

AF:

0.316

Gnomad ASJ exome

AF:

0.309

Gnomad EAS exome

AF:

0.319

Gnomad SAS exome

AF:

0.310

Gnomad FIN exome

AF:

0.195

Gnomad NFE exome

AF:

0.300

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.293

AC:

428783

AN:

1461766

Hom.:

64410

Cov.:

AF XY:

0.294

AC XY:

214148

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0669

Gnomad4 AMR exome

AF:

0.311

Gnomad4 ASJ exome

AF:

0.311

Gnomad4 EAS exome

AF:

0.300

Gnomad4 SAS exome

AF:

0.313

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.302

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.232

AC:

35323

AN:

152190

Hom.:

4910

Cov.:

AF XY:

0.230

AC XY:

17148

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0783

Gnomad4 AMR

AF:

0.312

Gnomad4 ASJ

AF:

0.317

Gnomad4 EAS

AF:

0.319

Gnomad4 SAS

AF:

0.319

Gnomad4 FIN

AF:

0.188

Gnomad4 NFE

AF:

0.297

Gnomad4 OTH

AF:

0.258

Alfa

AF:

0.268

Hom.:

2592

Bravo

AF:

0.234

Asia WGS

AF:

0.318

AC:

1106

AN:

3478

EpiCase

AF:

0.313

EpiControl

AF:

0.301

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.12

DANN

Benign

0.67

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