6-166158065-A-G

Variant names:

• chr6-166158065-A-G
• rs3816302
• NM_001366285.2:c.*250T>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.*250T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 613,300 control chromosomes in the GnomAD database, including 25,096 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 0.24 (4991 hom., cov: 33)
  • Exomes 𝑓: 0.29 (20105 hom.)
• Consequence: TBXT NM_001366285.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

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>C		3_prime_UTR	Exon 8 of 8	NP_001353214.1
	TBXT	NM_001366286.2		c.*250T>C		3_prime_UTR	Exon 9 of 9	NP_001353215.1
	TBXT	NM_003181.4		c.*250T>C		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>C		3_prime_UTR	Exon 8 of 8	ENSP00000355841.3
	TBXT	ENST00000366871.7	TSL:1	c.*250T>C		3_prime_UTR	Exon 8 of 8	ENSP00000355836.3
	TBXT	ENST00000296946.6	TSL:5	c.*250T>C		3_prime_UTR	Exon 9 of 9	ENSP00000296946.2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36134 AN: 152072 Hom.: 4990 Cov.: 33

Gnomad AFR AF: 0.0974

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.263

GnomAD4 exome AF: 0.290 AC: 133929 AN: 461110 Hom.: 20105 Cov.: 5 AF XY: 0.293 AC XY: 70661 AN XY: 241108

African (AFR) AF: 0.0942 AC: 1194 AN: 12680

American (AMR) AF: 0.310 AC: 5861 AN: 18902

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 4292 AN: 13690

East Asian (EAS) AF: 0.296 AC: 8963 AN: 30304

South Asian (SAS) AF: 0.314 AC: 14137 AN: 45046

European-Finnish (FIN) AF: 0.204 AC: 5794 AN: 28404

Middle Eastern (MID) AF: 0.306 AC: 600 AN: 1960

European-Non Finnish (NFE) AF: 0.301 AC: 85402 AN: 283884

Other (OTH) AF: 0.293 AC: 7686 AN: 26240

GnomAD4 genome AF: 0.237 AC: 36138 AN: 152190 Hom.: 4991 Cov.: 33 AF XY: 0.235 AC XY: 17517 AN XY: 74414

African (AFR) AF: 0.0971 AC: 4034 AN: 41540

American (AMR) AF: 0.312 AC: 4778 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3468

East Asian (EAS) AF: 0.319 AC: 1650 AN: 5166

South Asian (SAS) AF: 0.319 AC: 1541 AN: 4826

European-Finnish (FIN) AF: 0.188 AC: 1992 AN: 10608

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20221 AN: 67972

Other (OTH) AF: 0.263 AC: 556 AN: 2114

Alfa AF: 0.279 Hom.: 7712

Bravo AF: 0.240

Asia WGS AF: 0.319 AC: 1110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.18
DANN	Benign	0.41
PhyloP100		-1.4
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: rs3816302; hg19: chr6-166571553;