chr22-19766780-C-T
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001379200.1(TBX1):c.1428C>T(p.Ala476=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000675 in 1,333,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000067 ( 0 hom. )
Consequence
TBX1
NM_001379200.1 synonymous
NM_001379200.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.83
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 22-19766780-C-T is Benign according to our data. Variant chr22-19766780-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2183049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.83 with no splicing effect.
BS2
High AC in GnomAdExome4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX1 | NM_001379200.1 | c.1428C>T | p.Ala476= | synonymous_variant | 7/7 | ENST00000649276.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX1 | ENST00000649276.2 | c.1428C>T | p.Ala476= | synonymous_variant | 7/7 | NM_001379200.1 | A2 | ||
TBX1 | ENST00000332710.8 | c.1401C>T | p.Ala467= | synonymous_variant | 9/9 | 1 | P2 | ||
TBX1 | ENST00000329705.11 | c.1009+778C>T | intron_variant | 1 | A2 | ||||
TBX1 | ENST00000359500.7 | c.1009+778C>T | intron_variant | 1 | A2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000675 AC: 9AN: 1333480Hom.: 0 Cov.: 33 AF XY: 0.00000908 AC XY: 6AN XY: 660552
GnomAD4 exome
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33
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6
AN XY:
660552
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
DiGeorge syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 11, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 22, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at