Variant rs1247059195 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate

The ENST00000383701.8(EOGT):c.404G>A(p.Cys135Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C135S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

EOGT
ENST00000383701.8 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 6.52

Variant links:

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]

EOGT links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.965

PP5

Variant 3-69007729-C-T is Pathogenic according to our data. Variant chr3-69007729-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 523580.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EOGT	NM_001278689.2 linkuse as main transcript	c.404G>A	p.Cys135Tyr	missense_variant	6/18	ENST00000383701.8	NP_001265618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EOGT	ENST00000383701.8 linkuse as main transcript	c.404G>A	p.Cys135Tyr	missense_variant	6/18	1	NM_001278689.2	ENSP00000373206	P1	Q5NDL2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249258

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134822

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724656

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Adams-Oliver syndrome 4

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Dec 17, 2020	- -
Pathogenic, criteria provided, single submitter	research	Centre of Medical Genetics, University of Antwerp	Dec 01, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.45

BayesDel_noAF

Pathogenic

0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

T;.;T;.

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

.;.;T;T

M_CAP

Benign

0.026

MetaRNN

Pathogenic

0.96

D;D;D;D

MetaSVM

Uncertain

0.14

MutationAssessor

Uncertain

2.7

M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-9.8

D;D;.;.

REVEL

Uncertain

0.60

Sift

Uncertain

0.0010

D;D;.;.

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.98

MutPred

0.75

Gain of phosphorylation at C135 (P = 0.0534);Gain of phosphorylation at C135 (P = 0.0534);Gain of phosphorylation at C135 (P = 0.0534);Gain of phosphorylation at C135 (P = 0.0534);

MVP

0.38

MPC

0.82

ClinPred

1.0

GERP RS

5.1

Varity_R

0.92

gMVP

0.97

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