rs104894944
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_001109878.2(TBX22):c.352G>T(p.Gly118Cys) variant causes a missense change involving the alteration of a 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).
Frequency
Genomes: not found (cov: 22)
Consequence
TBX22
NM_001109878.2 missense
NM_001109878.2 missense
Scores
14
1
1
Clinical Significance
Conservation
PhyloP100: 8.75
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 Likely_pathogenic. Variant got 9 ACMG points.
PM1
?
In a DNA_binding_region T-box (size 187) in uniprot entity TBX22_HUMAN there are 9 pathogenic changes around while only 2 benign (82%) in NM_001109878.2
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.99
PP5
?
Variant X-80023236-G-T is Pathogenic according to our data. Variant chrX-80023236-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 11330.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-80023236-G-T is described in UniProt as null. Variant chrX-80023236-G-T is described in UniProt as null. Variant chrX-80023236-G-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX22 | NM_001109878.2 | c.352G>T | p.Gly118Cys | missense_variant | 3/9 | ENST00000373296.8 | |
TBX22 | NM_016954.2 | c.352G>T | p.Gly118Cys | missense_variant | 2/8 | ||
TBX22 | NM_001109879.2 | c.-5G>T | splice_region_variant, 5_prime_UTR_variant | 3/9 | |||
TBX22 | NM_001303475.1 | c.-72G>T | 5_prime_UTR_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX22 | ENST00000373296.8 | c.352G>T | p.Gly118Cys | missense_variant | 3/9 | 5 | NM_001109878.2 | P1 | |
TBX22 | ENST00000373294.8 | c.352G>T | p.Gly118Cys | missense_variant | 2/8 | 1 | P1 | ||
TBX22 | ENST00000626877.1 | n.168G>T | non_coding_transcript_exon_variant | 1/7 | 1 | ||||
TBX22 | ENST00000626498.2 | c.352G>T | p.Gly118Cys | missense_variant, splice_region_variant, NMD_transcript_variant | 3/9 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
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
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
A;A;A;A
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of methylation at R119 (P = 0.0452);Loss of methylation at R119 (P = 0.0452);
MVP
MPC
0.68
ClinPred
D
GERP RS
Varity_R
gMVP
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