chr3-68998059-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001278689.2(EOGT):c.783C>T(p.His261His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00534 in 1,601,624 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0055 ( 39 hom. )

Consequence

EOGT
NM_001278689.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.374

Publications

6 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 3-68998059-G-A is Benign according to our data. Variant chr3-68998059-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 376918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.374 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00379 (577/152278) while in subpopulation SAS AF = 0.00953 (46/4828). AF 95% confidence interval is 0.00734. There are 3 homozygotes in GnomAd4. There are 281 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EOGT	NM_001278689.2 link	c.783C>T	p.His261His	synonymous_variant	Exon 10 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.783C>T	p.His261His	synonymous_variant	Exon 10 of 18	1	NM_001278689.2	ENSP00000373206.3		Q5NDL2-1

Frequencies

GnomAD3 genomes

AF:

0.00379

AC:

576

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00931

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00585

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00463

AC:

1122

AN:

242154

AF XY:

0.00556

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.00151

Gnomad EAS exome

AF:

0.0000562

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.00508

Gnomad OTH exome

AF:

0.00546

GnomAD4 exome

AF:

0.00551

AC:

7983

AN:

1449346

Hom.:

Cov.:

AF XY:

0.00594

AC XY:

4287

AN XY:

721126

show subpopulations

African (AFR)

AF:

0.000879

AC:

AN:

32994

American (AMR)

AF:

0.00286

AC:

121

AN:

42302

Ashkenazi Jewish (ASJ)

AF:

0.00146

AC:

AN:

25968

East Asian (EAS)

AF:

0.000407

AC:

AN:

39276

South Asian (SAS)

AF:

0.0141

AC:

1179

AN:

83876

European-Finnish (FIN)

AF:

0.00146

AC:

AN:

53334

Middle Eastern (MID)

AF:

0.00747

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00564

AC:

6234

AN:

1105890

Other (OTH)

AF:

0.00409

AC:

245

AN:

59948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

351

703

1054

1406

1757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

236

472

708

944

1180

<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:

0.00379

AC:

577

AN:

152278

Hom.:

Cov.:

AF XY:

0.00377

AC XY:

281

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41558

American (AMR)

AF:

0.00301

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00953

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00585

AC:

398

AN:

68018

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

112

140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00465

Hom.:

Bravo

AF:

0.00379

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jul 08, 2016

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 11, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

EOGT: BP4, BP7, BS1, BS2 -

Adams-Oliver syndrome 4

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.9

(source)

DANN

Benign

0.78

PhyloP100

0.37

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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