chr6-166158065-A-G

Position:

• chr6-166158065-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000366876.7(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 ENST00000366876.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXT	NM_001366285.2	c.*250T>C		3_prime_UTR_variant	8/8	ENST00000366876.7	NP_001353214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXT	ENST00000366876.7	c.*250T>C		3_prime_UTR_variant	8/8	1	NM_001366285.2	ENSP00000355841	P4
TBXT	ENST00000366871.7	c.*250T>C		3_prime_UTR_variant	8/8	1		ENSP00000355836
TBXT	ENST00000296946.6	c.*250T>C		3_prime_UTR_variant	9/9	5		ENSP00000296946	A1

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

Gnomad4 AFR exome AF: 0.0942

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.314

Gnomad4 EAS exome AF: 0.296

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.204

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.293

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

Gnomad4 AFR AF: 0.0971

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.263

Alfa AF: 0.288 Hom.: 4046

Bravo AF: 0.240

Asia WGS AF: 0.319 AC: 1110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.18
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs3816302; hg19: chr6-166571553;