chr6-166160858-G-A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001366285.2(TBXT):c.1016C>T(p.Ala339Val) variant causes a missense change. The variant allele was found at a frequency of 0.00614 in 1,614,114 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A339A) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0047 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0063 ( 35 hom. )
Consequence
TBXT
NM_001366285.2 missense
NM_001366285.2 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 5.51
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0068078935).
BP6
?
Variant 6-166160858-G-A is Benign according to our data. Variant chr6-166160858-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd at 715 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBXT | NM_001366285.2 | c.1016C>T | p.Ala339Val | missense_variant | 7/8 | ENST00000366876.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBXT | ENST00000366876.7 | c.1016C>T | p.Ala339Val | missense_variant | 7/8 | 1 | NM_001366285.2 | P4 | |
TBXT | ENST00000366871.7 | c.839C>T | p.Ala280Val | missense_variant | 7/8 | 1 | |||
TBXT | ENST00000296946.6 | c.1013C>T | p.Ala338Val | missense_variant | 8/9 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00470 AC: 715AN: 152192Hom.: 5 Cov.: 33
GnomAD3 genomes
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715
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GnomAD3 exomes AF: 0.00503 AC: 1266AN: 251456Hom.: 9 AF XY: 0.00517 AC XY: 703AN XY: 135900
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GnomAD4 exome AF: 0.00629 AC: 9200AN: 1461804Hom.: 35 Cov.: 33 AF XY: 0.00621 AC XY: 4515AN XY: 727198
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GnomAD4 genome ? AF: 0.00469 AC: 715AN: 152310Hom.: 5 Cov.: 33 AF XY: 0.00498 AC XY: 371AN XY: 74482
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ESP6500AA
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 08, 2017 | - - |
TBXT-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 02, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Uncertain
T;T;.
Polyphen
B;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at