chr16-30086227-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_004608.4(TBX6):c.1309T>C(p.Ter437ArgextTer81) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
TBX6
NM_004608.4 stop_lost
NM_004608.4 stop_lost
Scores
1
2
4
Clinical Significance
Conservation
PhyloP100: 3.00
Genes affected
TBX6 (HGNC:11605): (T-box transcription factor 6) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. Knockout studies in mice indicate that this gene is important for specification of paraxial mesoderm structures. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 16-30086227-A-G is Pathogenic according to our data. Variant chr16-30086227-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3062294.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
?
Computational evidence support a benign effect (BayesDel_addAF=-0.0433196).. Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX6 | NM_004608.4 | c.1309T>C | p.Ter437ArgextTer81 | stop_lost | 9/9 | ENST00000395224.7 | |
TBX6 | XM_011545926.4 | c.1309T>C | p.Ter437ArgextTer81 | stop_lost | 9/9 | ||
TBX6 | XM_047434551.1 | c.1309T>C | p.Ter437ArgextTer81 | stop_lost | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX6 | ENST00000395224.7 | c.1309T>C | p.Ter437ArgextTer81 | stop_lost | 9/9 | 1 | NM_004608.4 | P1 | |
TBX6 | ENST00000279386.6 | c.1309T>C | p.Ter437ArgextTer81 | stop_lost | 8/8 | 1 | P1 | ||
TBX6 | ENST00000567664.5 | c.*443T>C | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spondylocostal dysostosis 5 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Molecular Genetics Department, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology | - | A previously undescribed nucleotide variant creates a p.Ter437ArgextTer81 in the TBX6 gene. The variant was observed in heterozygous state in an individual affected with multiple hemivertebra and short spine. Loss-of-function variants are reported in patients with Spondylocostal dysostosis 5, 122600. Another heterozygous variant causing stop-loss (c.1311A>T) was previously described in familial Spondylocostal dysostosis (OMIM: 122600, Spondylocostal dysostosis 5) [Sparrow et al., 2013, PMID: 23335591].The variant is not present in population database (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as likely pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
N;N
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.