22-19759638-GCAGGGATGCA-G
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The ENST00000332710.8(TBX1):c.-4_6del variant causes a start lost, 5 prime UTR change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
TBX1
ENST00000332710.8 start_lost, 5_prime_UTR
ENST00000332710.8 start_lost, 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.75
Genes affected
TBX1 (HGNC:11592): (T-box transcription factor 1) 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. This gene product shares 98% amino acid sequence identity with the mouse ortholog. DiGeorge syndrome (DGS)/velocardiofacial syndrome (VCFS), a common congenital disorder characterized by neural-crest-related developmental defects, has been associated with deletions of chromosome 22q11.2, where this gene has been mapped. Studies using mouse models of DiGeorge syndrome suggest a major role for this gene in the molecular etiology of DGS/VCFS. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX1 | NM_005992.1 | c.-4_6del | start_lost, 5_prime_UTR_variant | 2/10 | |||
TBX1 | NM_080646.2 | c.-4_6del | start_lost, 5_prime_UTR_variant | 2/9 | |||
TBX1 | NM_080647.1 | c.-4_6del | start_lost, 5_prime_UTR_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX1 | ENST00000329705.11 | c.-4_6del | start_lost, 5_prime_UTR_variant | 2/9 | 1 | A2 | |||
TBX1 | ENST00000332710.8 | c.-4_6del | start_lost, 5_prime_UTR_variant | 2/9 | 1 | P2 | |||
TBX1 | ENST00000359500.7 | c.-4_6del | start_lost, 5_prime_UTR_variant | 2/10 | 1 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
DiGeorge syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 17, 2022 | This variant has not been reported in the literature in individuals affected with TBX1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the TBX1 mRNA. The next in-frame methionine is located at codon 10. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.