rs3099266

Variant names:

• chr6-166167659-T-A
• rs3099266
• NM_001366285.2:c.-68A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-166167659-T-A
• chr6-166167659-T-C
• chr6-166167659-T-G

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.-68A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000725 in 1,378,804 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: TBXT NM_001366285.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 26 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, LIMITED Submitted by: PanelApp Australia, 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=-0.8).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXT	NM_001366285.2	MANE Select	c.-68A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001353214.1	J3KP65
	TBXT	NM_001366285.2	MANE Select	c.-68A>T		5_prime_UTR	Exon 1 of 8	NP_001353214.1	J3KP65
	TBXT	NM_001366286.2		c.-68A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_001353215.1	J3KP65

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXT	ENST00000366876.7	TSL:1 MANE Select	c.-68A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000355841.3	J3KP65
	TBXT	ENST00000366871.7	TSL:1	c.-68A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	ENSP00000355836.3	O15178-2
	TBXT	ENST00000366876.7	TSL:1 MANE Select	c.-68A>T		5_prime_UTR	Exon 1 of 8	ENSP00000355841.3	J3KP65

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.25e-7 AC: 1 AN: 1378804 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 680872

African (AFR) AF: 0.00 AC: 0 AN: 31444

American (AMR) AF: 0.0000280 AC: 1 AN: 35664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25136

East Asian (EAS) AF: 0.00 AC: 0 AN: 35694

South Asian (SAS) AF: 0.00 AC: 0 AN: 79108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34650

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4988

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074480

Other (OTH) AF: 0.00 AC: 0 AN: 57640

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 45037

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.70
PhyloP100		-0.046
PromoterAI		-0.0046	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3099266; hg19: chr6-166581147;