chr6-166158460-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001366285.2(TBXT):ā€‹c.1166A>Gā€‹(p.His389Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000085 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000068 ( 0 hom. )

Consequence

TBXT
NM_001366285.2 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13769251).
BS2
High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TBXTNM_001366285.2 linkuse as main transcriptc.1166A>G p.His389Arg missense_variant 8/8 ENST00000366876.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TBXTENST00000366876.7 linkuse as main transcriptc.1166A>G p.His389Arg missense_variant 8/81 NM_001366285.2 P4
TBXTENST00000366871.7 linkuse as main transcriptc.989A>G p.His330Arg missense_variant 8/81 O15178-2
TBXTENST00000296946.6 linkuse as main transcriptc.1163A>G p.His388Arg missense_variant 9/95 A1O15178-1

Frequencies

GnomAD3 genomes
AF:
0.0000855
AC:
13
AN:
152072
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
250878
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135732
show subpopulations
Gnomad AFR exome
AF:
0.000309
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461752
Hom.:
0
Cov.:
33
AF XY:
0.00000413
AC XY:
3
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000855
AC:
13
AN:
152072
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74272
show subpopulations
Gnomad4 AFR
AF:
0.000314
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000667
Hom.:
0
Bravo
AF:
0.0000869
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 07, 2023The c.1163A>G (p.H388R) alteration is located in exon 9 (coding exon 8) of the T gene. This alteration results from a A to G substitution at nucleotide position 1163, causing the histidine (H) at amino acid position 388 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
12
DANN
Benign
0.71
DEOGEN2
Benign
0.29
T;.;.
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.32
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.73
T;T;T
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-0.58
T
MutationTaster
Benign
0.88
D;D
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.1
N;N;N
REVEL
Benign
0.28
Sift
Benign
0.36
T;T;T
Sift4G
Benign
0.36
T;T;.
Polyphen
0.0020
B;.;.
Vest4
0.47
MVP
0.84
MPC
0.28
ClinPred
0.053
T
GERP RS
3.5
Varity_R
0.062
gMVP
0.49

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

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

Other links and lift over

dbSNP: rs139057807; hg19: chr6-166571948; API