6-166167659-T-C

Position:

• chr6-166167659-T-C

Variant summary

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

The ENST00000366876.7(TBXT):​c.-68A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 1,530,136 control chromosomes in the GnomAD database, including 286,021 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 0.66 (34063 hom., cov: 31)
  • Exomes 𝑓: 0.60 (251958 hom.)
• Consequence: TBXT ENST00000366876.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXT	NM_001366285.2	c.-68A>G		5_prime_UTR_variant	1/8	ENST00000366876.7	NP_001353214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXT	ENST00000366876.7	c.-68A>G		5_prime_UTR_variant	1/8	1	NM_001366285.2	ENSP00000355841	P4
TBXT	ENST00000366871.7	c.-68A>G		5_prime_UTR_variant	2/8	1		ENSP00000355836
TBXT	ENST00000296946.6	c.-68A>G		5_prime_UTR_variant	2/9	5		ENSP00000296946	A1
TBXT	ENST00000461348.2	c.-68A>G		5_prime_UTR_variant	2/6	5		ENSP00000453512

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100317 AN: 151792 Hom.: 34016 Cov.: 31

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.668

GnomAD4 exome AF: 0.602 AC: 830192 AN: 1378226 Hom.: 251958 Cov.: 30 AF XY: 0.602 AC XY: 409437 AN XY: 680628

Gnomad4 AFR exome AF: 0.831

Gnomad4 AMR exome AF: 0.636

Gnomad4 ASJ exome AF: 0.660

Gnomad4 EAS exome AF: 0.735

Gnomad4 SAS exome AF: 0.626

Gnomad4 FIN exome AF: 0.534

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.631

GnomAD4 genome AF: 0.661 AC: 100426 AN: 151910 Hom.: 34063 Cov.: 31 AF XY: 0.656 AC XY: 48676 AN XY: 74210

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.757

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.671

Alfa AF: 0.601 Hom.: 34112

Bravo AF: 0.678

Asia WGS AF: 0.749 AC: 2606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.5
DANN	Benign	0.64

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: rs3099266; hg19: chr6-166581147;