Variant 6-166160974-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.908-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000366876.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
TBXT	ENST00000366876.7 linkuse as main transcript	c.908-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_001366285.2	P4
TBXT	ENST00000366871.7 linkuse as main transcript	c.731-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1			O15178-2
TBXT	ENST00000296946.6 linkuse as main transcript	c.905-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5		A1	O15178-1

Frequencies

GnomAD3 genomes

AF:

0.0303

AC:

4615

AN:

152142

Hom.:

230

Cov.:

show subpopulations

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.:

AF XY:

0.00557

AC XY:

756

AN XY:

135738

show subpopulations

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.:

AF XY:

0.00260

AC XY:

1888

AN XY:

726970

show subpopulations

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.:

AF XY:

0.0290

AC XY:

2162

AN XY:

74442

show subpopulations

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.:

Bravo

AF:

0.0340

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over