chr22-19759605-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000332710.8(TBX1):c.-39C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,609,706 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00091 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0016 ( 8 hom. )
Consequence
TBX1
ENST00000332710.8 5_prime_UTR
ENST00000332710.8 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.11
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 22-19759605-C-T is Benign according to our data. Variant chr22-19759605-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 379734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-19759605-C-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000906 (138/152374) while in subpopulation SAS AF= 0.00869 (42/4832). AF 95% confidence interval is 0.00661. There are 1 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 138 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX1 | NM_005992.1 | c.-39C>T | 5_prime_UTR_variant | 2/10 | |||
TBX1 | NM_080646.2 | c.-39C>T | 5_prime_UTR_variant | 2/9 | |||
TBX1 | NM_080647.1 | c.-39C>T | 5_prime_UTR_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX1 | ENST00000329705.11 | c.-39C>T | 5_prime_UTR_variant | 2/9 | 1 | A2 | |||
TBX1 | ENST00000332710.8 | c.-39C>T | 5_prime_UTR_variant | 2/9 | 1 | P2 | |||
TBX1 | ENST00000359500.7 | c.-39C>T | 5_prime_UTR_variant | 2/10 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000906 AC: 138AN: 152256Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00194 AC: 466AN: 240380Hom.: 5 AF XY: 0.00247 AC XY: 324AN XY: 131240
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GnomAD4 exome AF: 0.00163 AC: 2380AN: 1457332Hom.: 8 Cov.: 34 AF XY: 0.00187 AC XY: 1352AN XY: 724886
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | TBX1: BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 26, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
DiGeorge syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at