rs3127334

Variant names:

• chr6-166160758-G-A
• rs3127334
• NM_001366285.2:c.1037+79C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-166160758-G-A
• chr6-166160758-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.92).
• 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 rank	MANE	Protein	UniProt
TBXT	NM_001366285.2	c.1037+79C>T		intron_variant	Intron 7 of 7	ENST00000366876.7	NP_001353214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBXT	ENST00000366876.7	c.1037+79C>T		intron_variant	Intron 7 of 7	1	NM_001366285.2	ENSP00000355841.3
TBXT	ENST00000366871.7	c.860+79C>T		intron_variant	Intron 7 of 7	1		ENSP00000355836.3
TBXT	ENST00000296946.6	c.1034+79C>T		intron_variant	Intron 8 of 8	5		ENSP00000296946.2

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

African (AFR) AF: 0.855 AC: 28391 AN: 33200

American (AMR) AF: 0.734 AC: 32507 AN: 44306

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 18474 AN: 25478

East Asian (EAS) AF: 0.875 AC: 34443 AN: 39378

South Asian (SAS) AF: 0.746 AC: 62924 AN: 84348

European-Finnish (FIN) AF: 0.673 AC: 35162 AN: 52270

Middle Eastern (MID) AF: 0.719 AC: 4084 AN: 5680

European-Non Finnish (NFE) AF: 0.737 AC: 810334 AN: 1099836

Other (OTH) AF: 0.759 AC: 45339 AN: 59706

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

African (AFR) AF: 0.849 AC: 35223 AN: 41486

American (AMR) AF: 0.727 AC: 11114 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2543 AN: 3472

East Asian (EAS) AF: 0.892 AC: 4613 AN: 5172

South Asian (SAS) AF: 0.758 AC: 3655 AN: 4824

European-Finnish (FIN) AF: 0.666 AC: 7017 AN: 10542

Middle Eastern (MID) AF: 0.690 AC: 200 AN: 290

European-Non Finnish (NFE) AF: 0.733 AC: 49841 AN: 67966

Other (OTH) AF: 0.756 AC: 1595 AN: 2110

Alfa AF: 0.756 Hom.: 6612

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

Nov 01, 2004

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.56
PhyloP100		0.35
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: rs3127334; hg19: chr6-166574246;