rs786204040
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_004608.4(TBX6):c.266_267insC(p.Val91GlyfsTer80) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
TBX6
NM_004608.4 frameshift
NM_004608.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.95
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 Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 16-30090844-C-CG is Pathogenic according to our data. Variant chr16-30090844-C-CG is described in ClinVar as [Pathogenic]. Clinvar id is 188055.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX6 | NM_004608.4 | c.266_267insC | p.Val91GlyfsTer80 | frameshift_variant | 3/9 | ENST00000395224.7 | |
TBX6 | XM_011545926.4 | c.266_267insC | p.Val91GlyfsTer80 | frameshift_variant | 3/9 | ||
TBX6 | XM_047434551.1 | c.266_267insC | p.Val91GlyfsTer80 | frameshift_variant | 2/8 | ||
TBX6 | XR_007064904.1 | n.389_390insC | non_coding_transcript_exon_variant | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX6 | ENST00000395224.7 | c.266_267insC | p.Val91GlyfsTer80 | frameshift_variant | 3/9 | 1 | NM_004608.4 | P1 | |
TBX6 | ENST00000279386.6 | c.266_267insC | p.Val91GlyfsTer80 | frameshift_variant | 2/8 | 1 | P1 | ||
TBX6 | ENST00000553607.1 | c.266_267insC | p.Val91GlyfsTer80 | frameshift_variant | 2/5 | 1 | |||
TBX6 | ENST00000567664.5 | c.266_267insC | p.Val91GlyfsTer80 | frameshift_variant, NMD_transcript_variant | 2/7 | 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: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spondylocostal dysostosis 5 Pathogenic:2
Pathogenic, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Nov 15, 2015 | This variant was observed in 1 individual with a vertebral malformation and rib abnormalities. The variant was found to be in trans with a high-risk TBX6 haplotype, T-C-A (rs2289292, rs3809624, rs3809627). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 22, 2015 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
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