6-166160974-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001366285.2(TBXT):c.908-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 1,613,648 control chromosomes in the GnomAD database, including 429 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (230 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (199 hom.)
• Consequence: TBXT NM_001366285.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002854
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.409

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-166160974-G-A is Benign according to our data. Variant chr6-166160974-G-A is described in ClinVar as [Benign]. Clinvar id is 768118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBXT	NM_001366285.2	c.908-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000366876.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBXT	ENST00000366876.7	c.908-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001366285.2	P4
TBXT	ENST00000366871.7	c.731-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
TBXT	ENST00000296946.6	c.905-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4615 AN: 152142 Hom.: 230 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00956

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0186

GnomAD3 exomes AF: 0.00768 AC: 1930 AN: 251202 Hom.: 90 AF XY: 0.00557 AC XY: 756 AN XY: 135738

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.00402

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00305 AC: 4451 AN: 1461388 Hom.: 199 Cov.: 33 AF XY: 0.00260 AC XY: 1888 AN XY: 726970

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.00497

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000827

Gnomad4 OTH exome AF: 0.00654

GnomAD4 genome AF: 0.0303 AC: 4616 AN: 152260 Hom.: 230 Cov.: 33 AF XY: 0.0290 AC XY: 2162 AN XY: 74442

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.00954

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0158 Hom.: 45

Bravo AF: 0.0340

Asia WGS AF: 0.00404 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.30
Dann	Benign	0.20

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000029
dbscSNV1_RF	Benign	0.0
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: rs61597882; hg19: chr6-166574462;