chr3-68977742-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001278689.2(EOGT):c.1460A>G(p.Glu487Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,612,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
EOGT
NM_001278689.2 missense
NM_001278689.2 missense
Scores
1
3
14
Clinical Significance
Conservation
PhyloP100: 6.20
Genes affected
EOGT (HGNC:28526): (EGF domain specific O-linked N-acetylglucosamine transferase) This gene encodes an enzyme that acts in the lumen of the endoplasmic reticulum to catalyze the transfer of N-acetylglucosamine to serine or threonine residues of extracellular-targeted proteins. This enzyme modifies proteins containing eukaryotic growth factor (EGF)-like domains, including the Notch receptor, thereby regulating developmental signalling. Mutations in this gene have been observed in individuals with Adams-Oliver syndrome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.29065946).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EOGT | NM_001278689.2 | c.1460A>G | p.Glu487Gly | missense_variant | 18/18 | ENST00000383701.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EOGT | ENST00000383701.8 | c.1460A>G | p.Glu487Gly | missense_variant | 18/18 | 1 | NM_001278689.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152122Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249678Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135014
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460788Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726676
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152122Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74292
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 24, 2023 | The c.1208A>G (p.E403G) alteration is located in exon 15 (coding exon 12) of the EOGT gene. This alteration results from a A to G substitution at nucleotide position 1208, causing the glutamic acid (E) at amino acid position 403 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Adams-Oliver syndrome 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 403 of the EOGT protein (p.Glu403Gly). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with EOGT-related conditions. ClinVar contains an entry for this variant (Variation ID: 2060583). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EOGT protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.;.
REVEL
Benign
Sift
Benign
T;T;.;.
Sift4G
Benign
T;T;T;T
Polyphen
P;P;P;P
Vest4
MutPred
Loss of solvent accessibility (P = 0.0387);.;Loss of solvent accessibility (P = 0.0387);.;
MVP
MPC
0.58
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at