NM_001366285.2:c.*250T>A

Variant names:

• chr6-166158065-A-T
• rs3816302
• NM_001366285.2:c.*250T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001366285.2(TBXT):​c.*250T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TBXT NM_001366285.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366285.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXT	NM_001366285.2	MANE Select	c.*250T>A		3_prime_UTR	Exon 8 of 8	NP_001353214.1
	TBXT	NM_001366286.2		c.*250T>A		3_prime_UTR	Exon 9 of 9	NP_001353215.1
	TBXT	NM_003181.4		c.*250T>A		3_prime_UTR	Exon 9 of 9	NP_003172.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXT	ENST00000366876.7	TSL:1 MANE Select	c.*250T>A		3_prime_UTR	Exon 8 of 8	ENSP00000355841.3
	TBXT	ENST00000366871.7	TSL:1	c.*250T>A		3_prime_UTR	Exon 8 of 8	ENSP00000355836.3
	TBXT	ENST00000296946.6	TSL:5	c.*250T>A		3_prime_UTR	Exon 9 of 9	ENSP00000296946.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 461892 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 241554

African (AFR) AF: 0.00 AC: 0 AN: 12696

American (AMR) AF: 0.00 AC: 0 AN: 18926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13710

East Asian (EAS) AF: 0.00 AC: 0 AN: 30352

South Asian (SAS) AF: 0.00 AC: 0 AN: 45110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1964

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 284408

Other (OTH) AF: 0.00 AC: 0 AN: 26276

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.46
PhyloP100		-1.4

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: rs3816302; hg19: chr6-166571553;