chr22-19766434-C-T
Variant summary
Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_001379200.1(TBX1):c.1082C>T(p.Pro361Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,349,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P361A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001379200.1 missense
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 -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TBX1 | NM_001379200.1 | c.1082C>T | p.Pro361Leu | missense_variant | Exon 7 of 7 | ENST00000649276.2 | NP_001366129.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TBX1 | ENST00000649276.2 | c.1082C>T | p.Pro361Leu | missense_variant | Exon 7 of 7 | NM_001379200.1 | ENSP00000497003.1 |
Frequencies
GnomAD3 genomes AF: 0.0000463 AC: 7AN: 151314Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000997 AC: 4AN: 40124 AF XY: 0.0000423 show subpopulations
GnomAD4 exome AF: 0.0000367 AC: 44AN: 1198006Hom.: 0 Cov.: 23 AF XY: 0.0000256 AC XY: 15AN XY: 586930 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000463 AC: 7AN: 151314Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 73888 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
DiGeorge syndrome Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 352 of the TBX1 protein (p.Pro352Leu). This variant is present in population databases (no rsID available, gnomAD 0.02%). This missense change has been observed in individual(s) with TBX1-related conditions (internal data). This missense change has been observed in at least one individual who was not affected with TBX1-related conditions (internal data). ClinVar contains an entry for this variant (Variation ID: 573382). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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
In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31428446) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at