Genetic Variant EOGT:p.Lys188Glu (chr3-69004436-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001278689.2(EOGT):c.562A>G(p.Lys188Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K188L) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EOGT
NM_001278689.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.862

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Adams-Oliver syndrome 4
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
Adams-Oliver syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EOGT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12548506).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278689.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EOGT	NM_001278689.2	MANE Select	c.562A>G	p.Lys188Glu	missense	Exon 8 of 18	NP_001265618.1
EOGT	NM_173654.3		c.562A>G	p.Lys188Glu	missense	Exon 8 of 15	NP_775925.1
EOGT	NR_103826.2		n.1028A>G		non_coding_transcript_exon	Exon 8 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EOGT	ENST00000383701.8	TSL:1 MANE Select	c.562A>G	p.Lys188Glu	missense	Exon 8 of 18	ENSP00000373206.3
EOGT	ENST00000295571.9	TSL:1	c.562A>G	p.Lys188Glu	missense	Exon 8 of 15	ENSP00000295571.5
EOGT	ENST00000894422.1		c.562A>G	p.Lys188Glu	missense	Exon 7 of 17	ENSP00000564481.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111968

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.0095

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.54

M_CAP

Benign

0.0050

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.3

PhyloP100

0.86

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.57

REVEL

Benign

0.064

Sift

Benign

0.34

Sift4G

Benign

0.71

Polyphen

0.0030

Vest4

0.23

MutPred

0.57

Loss of methylation at K188 (P = 0.0127)

MVP

0.11

MPC

0.20

ClinPred

0.045

GERP RS

-0.90

Varity_R

0.036

gMVP

0.54

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over