22-19759605-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_080647.1(TBX1):c.-39C>T variant causes a 5 prime UTR premature start codon gain 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
NM_080647.1 5_prime_UTR_premature_start_codon_gain
NM_080647.1 5_prime_UTR_premature_start_codon_gain
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 GnomAd4 at 138 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TBX1 | NM_080647.1 | c.-39C>T | 5_prime_UTR_premature_start_codon_gain_variant | 2/9 | NP_542378.1 | |||
TBX1 | NM_080646.2 | c.-39C>T | 5_prime_UTR_premature_start_codon_gain_variant | 2/9 | NP_542377.1 | |||
TBX1 | NM_005992.1 | c.-39C>T | 5_prime_UTR_premature_start_codon_gain_variant | 2/10 | NP_005983.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TBX1 | ENST00000332710 | c.-39C>T | 5_prime_UTR_premature_start_codon_gain_variant | 2/9 | 1 | ENSP00000331791.4 | ||||
TBX1 | ENST00000329705 | c.-39C>T | 5_prime_UTR_premature_start_codon_gain_variant | 2/9 | 1 | ENSP00000331176.7 | ||||
TBX1 | ENST00000359500 | c.-39C>T | 5_prime_UTR_premature_start_codon_gain_variant | 2/10 | 1 | ENSP00000352483.3 |
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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GnomAD4 genome AF: 0.000906 AC: 138AN: 152374Hom.: 1 Cov.: 33 AF XY: 0.000953 AC XY: 71AN XY: 74512
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2024 | TBX1: BS2 - |
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 | Labcorp Genetics (formerly Invitae), Labcorp | Jan 08, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at