X-71538030-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_181672.3(OGT):​c.420A>T​(p.Glu140Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Consequence

OGT
NM_181672.3 missense

Scores

1
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.63
Variant links:
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), OGT. . Gene score misZ: 5.6667 (greater than the threshold 3.09). The gene has 12 curated pathogenic missense variants (we use a threshold of 10). The gene has 3 curated benign missense variants. GenCC has associacion of the gene with intellectual disability, X-linked 106.
BP4
Computational evidence support a benign effect (MetaRNN=0.38319108).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OGTNM_181672.3 linkc.420A>T p.Glu140Asp missense_variant 3/22 ENST00000373719.8 NP_858058.1 O15294-1
OGTNM_181673.3 linkc.390A>T p.Glu130Asp missense_variant 3/22 NP_858059.1 O15294-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OGTENST00000373719.8 linkc.420A>T p.Glu140Asp missense_variant 3/221 NM_181672.3 ENSP00000362824.3 O15294-1

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
24

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Intellectual disability, X-linked 106 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingBaylor GeneticsOct 18, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.061
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.29
T;.;T
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.93
D;D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.38
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.99
L;.;.
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-1.3
N;N;N
REVEL
Benign
0.24
Sift
Benign
0.18
T;T;T
Sift4G
Benign
0.12
T;T;T
Polyphen
0.0020
B;B;.
Vest4
0.56
MutPred
0.38
Gain of relative solvent accessibility (P = 0.1894);.;.;
MVP
0.86
MPC
1.3
ClinPred
0.79
D
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.47
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2040191879; hg19: chrX-70757880; API