X-71536278-G-C

Variant names:

• chrX-71536278-G-C
• NM_181672.3:c.138G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_181672.3(OGT):​c.138G>C​(p.Gln46His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: OGT NM_181672.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.59

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the OGT gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 12 curated pathogenic missense variants (we use a threshold of 10). The gene has 3 curated benign missense variants. Gene score misZ: 5.6667 (above the threshold of 3.09). GenCC associations: The gene is linked to intellectual disability, X-linked 106.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OGT	NM_181672.3	c.138G>C	p.Gln46His	missense_variant	Exon 2 of 22	ENST00000373719.8	NP_858058.1
OGT	NM_181673.3	c.108G>C	p.Gln36His	missense_variant	Exon 2 of 22		NP_858059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OGT	ENST00000373719.8	c.138G>C	p.Gln46His	missense_variant	Exon 2 of 22	1	NM_181672.3	ENSP00000362824.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jul 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.138G>C (p.Q46H) alteration is located in exon 2 (coding exon 2) of the OGT gene. This alteration results from a G to C substitution at nucleotide position 138, causing the glutamine (Q) at amino acid position 46 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.44	T;.;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Uncertain	0.092	D
MutationAssessor	Uncertain	2.4	M;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-2.3	N;N;D
REVEL	Benign	0.22
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.54	T;T;T
Polyphen		0.90	P;D;.
Vest4		0.54
MutPred		0.34		Gain of helix (P = 0.132);.;.;
MVP		0.88
MPC		1.5
ClinPred		0.91	D
GERP RS		5.2
Varity_R		0.75
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-70756128;