rs1131692155
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PS1PM2PP2PP3_ModeratePP5
The NM_181672.3(OGT):c.762G>C(p.Leu254Phe) variant causes a missense 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). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin ClinVar.
Frequency
Genomes: not found (cov: 21)
Consequence
OGT
NM_181672.3 missense
NM_181672.3 missense
Scores
6
9
2
Clinical Significance
Conservation
PhyloP100: 2.70
Genes affected
OGT (HGNC:8127): (O-linked N-acetylglucosamine (GlcNAc) transferase) This gene encodes a glycosyltransferase that catalyzes the addition of a single N-acetylglucosamine in O-glycosidic linkage to serine or threonine residues. Since both phosphorylation and glycosylation compete for similar serine or threonine residues, the two processes may compete for sites, or they may alter the substrate specificity of nearby sites by steric or electrostatic effects. The protein contains multiple tetratricopeptide repeats that are required for optimal recognition of substrates. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PS1
?
Transcript NM_181672.3 (OGT) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar as 428570
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, OGT
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.861
PP5
?
Variant X-71555223-G-C is Pathogenic according to our data. Variant chrX-71555223-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 804282.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OGT | NM_181672.3 | c.762G>C | p.Leu254Phe | missense_variant | 7/22 | ENST00000373719.8 | |
OGT | NM_181673.3 | c.732G>C | p.Leu244Phe | missense_variant | 7/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OGT | ENST00000373719.8 | c.762G>C | p.Leu254Phe | missense_variant | 7/22 | 1 | NM_181672.3 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 21
GnomAD3 genomes
?
Cov.:
21
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 21
GnomAD4 genome
?
Cov.:
21
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Intellectual disability, X-linked 106 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | Daan van Aalten Lab, University of Dundee | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Pathogenic
D;.
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of helix (P = 0.1706);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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