rs3127334

chr6-166160758-G-Achr6-166160758-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366285.2(TBXT):c.1037+79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 1,596,264 control chromosomes in the GnomAD database, including 443,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.77 (44859 hom., cov: 31)
  • Exomes 𝑓: 0.74 (398830 hom.)
• Consequence: TBXT NM_001366285.2 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 0.346

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBXT	NM_001366285.2	c.1037+79C>T		intron_variant		ENST00000366876.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXT	ENST00000366876.7	c.1037+79C>T		intron_variant		1	NM_001366285.2	P4
TBXT	ENST00000366871.7	c.860+79C>T		intron_variant		1
TBXT	ENST00000296946.6	c.1034+79C>T		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116260 AN: 151944 Hom.: 44810 Cov.: 31

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.752

GnomAD4 exome AF: 0.742 AC: 1071658 AN: 1444202 Hom.: 398830 AF XY: 0.740 AC XY: 530950 AN XY: 717190

Gnomad4 AFR exome AF: 0.855

Gnomad4 AMR exome AF: 0.734

Gnomad4 ASJ exome AF: 0.725

Gnomad4 EAS exome AF: 0.875

Gnomad4 SAS exome AF: 0.746

Gnomad4 FIN exome AF: 0.673

Gnomad4 NFE exome AF: 0.737

Gnomad4 OTH exome AF: 0.759

GnomAD4 genome AF: 0.765 AC: 116369 AN: 152062 Hom.: 44859 Cov.: 31 AF XY: 0.762 AC XY: 56649 AN XY: 74326

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.892

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.756

Alfa AF: 0.754 Hom.: 6341

Bravo AF: 0.776

Asia WGS AF: 0.840 AC: 2921 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Neural tube defects, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Nov 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.1
Dann	Benign	0.56

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

Other links and lift over

dbSNP: rs3127334; hg19: chr6-166574246;