Variant X-71533333-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_181672.3(OGT):c.34A>C(p.Thr12Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000167 in 1,194,317 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

OGT
NM_181672.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.92

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]

OGT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGT	NM_181672.3 link	c.34A>C	p.Thr12Pro	missense_variant	1/22	ENST00000373719.8	NP_858058.1	O15294-1
OGT	NM_181673.3 link	c.34A>C	p.Thr12Pro	missense_variant	1/22		NP_858059.1	O15294-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OGT	ENST00000373719.8 link	c.34A>C	p.Thr12Pro	missense_variant	1/22	1	NM_181672.3	ENSP00000362824.3		O15294-1

Frequencies

GnomAD3 genomes

AF:

0.00000900

AC:

AN:

111161

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33345

show subpopulations

Gnomad AFR

AF:

0.0000328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.23e-7

AC:

AN:

1083156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

352912

show subpopulations

Gnomad4 AFR exome

AF:

0.0000383

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000900

AC:

AN:

111161

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33345

show subpopulations

Gnomad4 AFR

AF:

0.0000328

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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 submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 13, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;.

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.67

T;T

M_CAP

Pathogenic

0.54

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.1

L;L

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.47

N;N

REVEL

Uncertain

0.50

Sift

Benign

0.032

D;T

Sift4G

Benign

0.13

T;T

Polyphen

0.95

P;D

Vest4

0.53

MutPred

0.37

Gain of relative solvent accessibility (P = 0.0289);Gain of relative solvent accessibility (P = 0.0289);

MVP

0.97

MPC

1.8

ClinPred

0.91

GERP RS

5.1

Varity_R

0.47

gMVP

0.73

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over