chr6-166157955-C-T

Variant names:

• chr6-166157955-C-T
• rs1056053
• NM_001366285.2:c.*360G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366285.2(TBXT):​c.*360G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 371,254 control chromosomes in the GnomAD database, including 78,732 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.67 (34459 hom., cov: 32)
  • Exomes 𝑓: 0.63 (44273 hom.)
• Consequence: TBXT NM_001366285.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• chordoma

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBXT	NM_001366285.2	c.*360G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000366876.7	NP_001353214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXT	ENST00000366876.7	c.*360G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_001366285.2	ENSP00000355841.3
TBXT	ENST00000366871.7	c.*360G>A		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000355836.3
TBXT	ENST00000296946.6	c.*360G>A		3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000296946.2

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101432 AN: 151934 Hom.: 34434 Cov.: 32

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.675

GnomAD4 exome AF: 0.630 AC: 138009 AN: 219202 Hom.: 44273 Cov.: 0 AF XY: 0.628 AC XY: 72676 AN XY: 115690

African (AFR) AF: 0.787 AC: 5491 AN: 6978

American (AMR) AF: 0.650 AC: 6611 AN: 10170

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 4054 AN: 6224

East Asian (EAS) AF: 0.833 AC: 9505 AN: 11408

South Asian (SAS) AF: 0.623 AC: 19836 AN: 31842

European-Finnish (FIN) AF: 0.554 AC: 6025 AN: 10884

Middle Eastern (MID) AF: 0.633 AC: 570 AN: 900

European-Non Finnish (NFE) AF: 0.607 AC: 78075 AN: 128620

Other (OTH) AF: 0.644 AC: 7842 AN: 12176

GnomAD4 genome AF: 0.668 AC: 101516 AN: 152052 Hom.: 34459 Cov.: 32 AF XY: 0.665 AC XY: 49381 AN XY: 74306

African (AFR) AF: 0.785 AC: 32553 AN: 41492

American (AMR) AF: 0.643 AC: 9820 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2314 AN: 3470

East Asian (EAS) AF: 0.842 AC: 4350 AN: 5166

South Asian (SAS) AF: 0.639 AC: 3084 AN: 4826

European-Finnish (FIN) AF: 0.547 AC: 5768 AN: 10538

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41510 AN: 67966

Other (OTH) AF: 0.678 AC: 1432 AN: 2112

Alfa AF: 0.640 Hom.: 80222

Bravo AF: 0.684

Asia WGS AF: 0.775 AC: 2695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.97
DANN	Benign	0.75
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1056053; hg19: chr6-166571443;