chrX-80022435-G-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001109878.2(TBX22):c.166G>T(p.Glu56Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 22)
Consequence
TBX22
NM_001109878.2 stop_gained
NM_001109878.2 stop_gained
Scores
1
2
2
Clinical Significance
Conservation
PhyloP100: -0.382
Genes affected
TBX22 (HGNC:11600): (T-box transcription factor 22) 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. Mutations in this gene have been associated with the inherited X-linked disorder, Cleft palate with ankyloglossia, and it is believed to play a major role in human palatogenesis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-80022435-G-T is Pathogenic according to our data. Variant chrX-80022435-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 11333.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-80022435-G-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX22 | NM_001109878.2 | c.166G>T | p.Glu56Ter | stop_gained | 2/9 | ENST00000373296.8 | |
TBX22 | NM_016954.2 | c.166G>T | p.Glu56Ter | stop_gained | 1/8 | ||
TBX22 | NM_001109879.2 | c.-191G>T | 5_prime_UTR_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX22 | ENST00000373296.8 | c.166G>T | p.Glu56Ter | stop_gained | 2/9 | 5 | NM_001109878.2 | P1 | |
TBX22 | ENST00000373294.8 | c.166G>T | p.Glu56Ter | stop_gained | 1/8 | 1 | P1 | ||
TBX22 | ENST00000476373.1 | n.287G>T | non_coding_transcript_exon_variant | 2/2 | 3 | ||||
TBX22 | ENST00000626498.2 | c.166G>T | p.Glu56Ter | stop_gained, NMD_transcript_variant | 2/9 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Cleft palate with ankyloglossia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2001 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at