6-166162299-C-T

Position:

• chr6-166162299-C-T

Variant summary

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

The NM_001366285.2(TBXT):​c.907+148G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 809,002 control chromosomes in the GnomAD database, including 11,928 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 0.18 (3332 hom., cov: 32)
  • Exomes 𝑓: 0.13 (8596 hom.)
• Consequence: TBXT NM_001366285.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

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 (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBXT	NM_001366285.2	c.907+148G>A		intron_variant		ENST00000366876.7	NP_001353214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBXT	ENST00000366876.7	c.907+148G>A		intron_variant		1	NM_001366285.2	ENSP00000355841	P4
TBXT	ENST00000366871.7	c.731-1333G>A		intron_variant		1		ENSP00000355836
TBXT	ENST00000296946.6	c.904+148G>A		intron_variant		5		ENSP00000296946	A1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27172 AN: 152020 Hom.: 3335 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0977

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.128 AC: 84080 AN: 656864 Hom.: 8596 AF XY: 0.125 AC XY: 42750 AN XY: 341430

Gnomad4 AFR exome AF: 0.323

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.0724

Gnomad4 EAS exome AF: 0.501

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.0952

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.179 AC: 27188 AN: 152138 Hom.: 3332 Cov.: 32 AF XY: 0.182 AC XY: 13516 AN XY: 74404

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.0977

Gnomad4 OTH AF: 0.154

Alfa AF: 0.124 Hom.: 814

Bravo AF: 0.186

Asia WGS AF: 0.283 AC: 985 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	1.7
DANN	Benign	0.59

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: rs2278677; hg19: chr6-166575787;