rs116138787

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001278689.2(EOGT):c.563A>T(p.Lys188Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,614,114 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K188L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0084 ( 19 hom., cov: 31)

Exomes 𝑓: 0.00099 ( 21 hom. )

Consequence

EOGT
NM_001278689.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.13

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00980404).

BP6

Variant 3-69004435-T-A is Benign according to our data. Variant chr3-69004435-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 445295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00835 (1272/152296) while in subpopulation AFR AF = 0.0284 (1182/41564). AF 95% confidence interval is 0.0271. There are 19 homozygotes in GnomAd4. There are 614 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EOGT	NM_001278689.2 link	c.563A>T	p.Lys188Ile	missense_variant	Exon 8 of 18	ENST00000383701.8	NP_001265618.1	Q5NDL2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EOGT	ENST00000383701.8 link	c.563A>T	p.Lys188Ile	missense_variant	Exon 8 of 18	1	NM_001278689.2	ENSP00000373206.3		Q5NDL2-1

Frequencies

GnomAD3 genomes

AF:

0.00836

AC:

1272

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00230

AC:

578

AN:

251450

AF XY:

0.00180

show subpopulations

Gnomad AFR exome

AF:

0.0278

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000814

GnomAD4 exome

AF:

0.000991

AC:

1448

AN:

1461818

Hom.:

Cov.:

AF XY:

0.000949

AC XY:

690

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.0299

AC:

999

AN:

33458

American (AMR)

AF:

0.00195

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:

0.00161

AC:

139

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000109

AC:

121

AN:

1111970

Other (OTH)

AF:

0.00151

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

139

209

278

348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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

AF:

0.00835

AC:

1272

AN:

152296

Hom.:

Cov.:

AF XY:

0.00824

AC XY:

614

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0284

AC:

1182

AN:

41564

American (AMR)

AF:

0.00353

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00270

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68030

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

118

177

236

295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00144

Hom.:

Bravo

AF:

0.00955

ESP6500AA

AF:

0.0225

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00273

AC:

331

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 27, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 18, 2024

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.11

T;.;T;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.90

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.70

.;.;T;T

MetaRNN

Benign

0.0098

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.3

L;L;L;L

PhyloP100

1.1

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-4.2

D;D;.;.

REVEL

Benign

0.080

Sift

Benign

0.057

T;T;.;.

Sift4G

Benign

0.14

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.41

MVP

0.19

MPC

0.26

ClinPred

0.046

GERP RS

-1.8

Varity_R

0.075

gMVP

0.63

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over