chr22-19759683-C-T
Variant summary
Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2
The ENST00000332710.8(TBX1):c.34+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
ENST00000332710.8 splice_region, intron
Scores
Clinical Significance
Conservation
Publications
- conotruncal heart malformationsInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- DiGeorge syndromeInheritance: AD Classification: DEFINITIVE Submitted by: G2P
- velocardiofacial syndromeInheritance: AD Classification: STRONG Submitted by: Ambry Genetics
- 22q11.2 deletion syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TBX1 | NM_080647.1 | c.34+6C>T | splice_region_variant, intron_variant | Intron 2 of 8 | NP_542378.1 | |||
TBX1 | NM_080646.2 | c.34+6C>T | splice_region_variant, intron_variant | Intron 2 of 8 | NP_542377.1 | |||
TBX1 | NM_005992.1 | c.34+6C>T | splice_region_variant, intron_variant | Intron 2 of 9 | NP_005983.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TBX1 | ENST00000332710.8 | c.34+6C>T | splice_region_variant, intron_variant | Intron 2 of 8 | 1 | ENSP00000331791.4 | ||||
TBX1 | ENST00000329705.11 | c.34+6C>T | splice_region_variant, intron_variant | Intron 2 of 8 | 1 | ENSP00000331176.7 | ||||
TBX1 | ENST00000359500.7 | c.34+6C>T | splice_region_variant, intron_variant | Intron 2 of 9 | 1 | ENSP00000352483.3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152256Hom.: 0 Cov.: 33 show subpopulations
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1459978Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3AN XY: 726254 show subpopulations
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152256Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74384 show subpopulations
ClinVar
Submissions by phenotype
DiGeorge syndrome Uncertain:1
ClinVar contains an entry for this variant (Variation ID: 1018677). This variant has not been reported in the literature in individuals affected with TBX1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change falls in intron 2 of the TBX1 gene. It does not directly change the encoded amino acid sequence of the TBX1 protein. It affects a nucleotide within the consensus splice site. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. -
not provided Uncertain:1
TBX1: PM2, BP4 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at