rs1056048

Variant names:

• chr6-166166700-G-A
• rs1056048
• NM_001366285.2:c.363C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-166166700-G-A
• chr6-166166700-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001366285.2(TBXT):​c.363C>T​(p.Ser121Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.212 in 1,613,756 control chromosomes in the GnomAD database, including 38,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5169 hom., cov: 33)
  • Exomes 𝑓: 0.21 (33268 hom.)
• Consequence: TBXT NM_001366285.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 3.79
• Publications: 11 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 6-166166700-G-A is Benign according to our data. Variant chr6-166166700-G-A is described in ClinVar as Benign. ClinVar VariationId is 1302242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXT	NM_001366285.2	MANE Select	c.363C>T	p.Ser121Ser	synonymous	Exon 2 of 8	NP_001353214.1
	TBXT	NM_001366286.2		c.363C>T	p.Ser121Ser	synonymous	Exon 3 of 9	NP_001353215.1
	TBXT	NM_003181.4		c.363C>T	p.Ser121Ser	synonymous	Exon 3 of 9	NP_003172.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBXT	ENST00000366876.7	TSL:1 MANE Select	c.363C>T	p.Ser121Ser	synonymous	Exon 2 of 8	ENSP00000355841.3
	TBXT	ENST00000366871.7	TSL:1	c.363C>T	p.Ser121Ser	synonymous	Exon 3 of 8	ENSP00000355836.3
	TBXT	ENST00000296946.6	TSL:5	c.363C>T	p.Ser121Ser	synonymous	Exon 3 of 9	ENSP00000296946.2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37469 AN: 152056 Hom.: 5152 Cov.: 33

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.0419

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.257

GnomAD2 exomes AF: 0.209 AC: 52338 AN: 250998 AF XY: 0.204

Gnomad AFR exome AF: 0.363

Gnomad AMR exome AF: 0.235

Gnomad ASJ exome AF: 0.259

Gnomad EAS exome AF: 0.0328

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.208 AC: 304206 AN: 1461582 Hom.: 33268 Cov.: 39 AF XY: 0.206 AC XY: 150140 AN XY: 727118

African (AFR) AF: 0.370 AC: 12403 AN: 33480

American (AMR) AF: 0.233 AC: 10433 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 6884 AN: 26136

East Asian (EAS) AF: 0.0340 AC: 1350 AN: 39700

South Asian (SAS) AF: 0.188 AC: 16227 AN: 86256

European-Finnish (FIN) AF: 0.176 AC: 9349 AN: 53112

Middle Eastern (MID) AF: 0.238 AC: 1375 AN: 5768

European-Non Finnish (NFE) AF: 0.210 AC: 233310 AN: 1112010

Other (OTH) AF: 0.213 AC: 12875 AN: 60396

GnomAD4 genome AF: 0.247 AC: 37540 AN: 152174 Hom.: 5169 Cov.: 33 AF XY: 0.241 AC XY: 17906 AN XY: 74406

African (AFR) AF: 0.369 AC: 15328 AN: 41506

American (AMR) AF: 0.206 AC: 3149 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 922 AN: 3472

East Asian (EAS) AF: 0.0422 AC: 219 AN: 5192

South Asian (SAS) AF: 0.176 AC: 852 AN: 4828

European-Finnish (FIN) AF: 0.172 AC: 1820 AN: 10588

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14435 AN: 67990

Other (OTH) AF: 0.258 AC: 545 AN: 2112

Alfa AF: 0.212 Hom.: 1732

Bravo AF: 0.256

Asia WGS AF: 0.163 AC: 567 AN: 3478

EpiCase AF: 0.216

EpiControl AF: 0.220

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	TBXT-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		3.8
Mutation Taster		=81/19	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: rs1056048; hg19: chr6-166580188; COSMIC: COSV51618311;