chr22-19759682-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The ENST00000332710.8(TBX1):c.34+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,459,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000332710.8 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX1 | NM_005992.1 | c.34+5G>A | splice_donor_5th_base_variant, intron_variant | ||||
TBX1 | NM_080646.2 | c.34+5G>A | splice_donor_5th_base_variant, intron_variant | ||||
TBX1 | NM_080647.1 | c.34+5G>A | splice_donor_5th_base_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX1 | ENST00000329705.11 | c.34+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | A2 | ||||
TBX1 | ENST00000332710.8 | c.34+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | P2 | ||||
TBX1 | ENST00000359500.7 | c.34+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1459958Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 726242
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 26, 2018 | The c.34+5G>A variant in the TBX1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant reduces the quality of the splice donor site in intron 2, and is expected to cause abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of the c.34+5G>A change in this individual is unknown. The c.34+5G>A variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.34+5G>A as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at