chrX-71536280-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate

The NM_181672.3(OGT):​c.140T>G​(p.Leu47Arg) 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Consequence

OGT
NM_181672.3 missense

Scores

9
7
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.75
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 5 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). GenCC has associacion of gene with intellectual disability, X-linked 106.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OGTNM_181672.3 linkuse as main transcriptc.140T>G p.Leu47Arg missense_variant 2/22 ENST00000373719.8 NP_858058.1
OGTNM_181673.3 linkuse as main transcriptc.110T>G p.Leu37Arg missense_variant 2/22 NP_858059.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OGTENST00000373719.8 linkuse as main transcriptc.140T>G p.Leu47Arg missense_variant 2/221 NM_181672.3 ENSP00000362824 P3O15294-1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
23

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 GeneticsJan 12, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.45
D
BayesDel_noAF
Pathogenic
0.41
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.73
D;.;T
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Pathogenic
0.65
D
MetaRNN
Pathogenic
0.88
D;D;D
MetaSVM
Uncertain
0.041
D
MutationAssessor
Uncertain
2.4
M;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.93
D
PROVEAN
Uncertain
-3.8
D;D;D
REVEL
Pathogenic
0.66
Sift
Uncertain
0.0030
D;D;D
Sift4G
Uncertain
0.0060
D;D;D
Polyphen
0.99
D;D;.
Vest4
0.91
MutPred
0.74
Gain of disorder (P = 0.0357);.;.;
MVP
0.99
MPC
2.8
ClinPred
0.99
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.94
gMVP
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-70756130; API