Variant chr3-68982812-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001278689.2(EOGT):c.1213A>G(p.Arg405Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0163 in 1,605,510 control chromosomes in the GnomAD database, including 1,197 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 212 hom., cov: 32)

Exomes 𝑓: 0.016 ( 985 hom. )

Consequence

EOGT
NM_001278689.2 missense, splice_region

Scores

Splicing: ADA: 0.7601

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.16

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:

EOGT (HGNC:):

EOGT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015622377).

BP6

Variant 3-68982812-T-C is Benign according to our data. Variant chr3-68982812-T-C is described in ClinVar as [Benign]. Clinvar id is 474283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EOGT	NM_001278689.2 linkuse as main transcript	c.1213A>G	p.Arg405Gly	missense_variant, splice_region_variant	15/18	ENST00000383701.8	NP_001265618.1	Q5NDL2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EOGT	ENST00000383701.8 linkuse as main transcript	c.1213A>G	p.Arg405Gly	missense_variant, splice_region_variant	15/18	1	NM_001278689.2	ENSP00000373206.3		Q5NDL2-1

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3327

AN:

152160

Hom.:

210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00492

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.0354

Gnomad EAS

AF:

0.0125

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.0253

GnomAD3 exomes

AF:

0.0353

AC:

8662

AN:

245562

Hom.:

691

AF XY:

0.0294

AC XY:

3901

AN XY:

132728

show subpopulations

Gnomad AFR exome

AF:

0.00457

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.0264

Gnomad EAS exome

AF:

0.0129

Gnomad SAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.00311

Gnomad NFE exome

AF:

0.00949

Gnomad OTH exome

AF:

0.0281

GnomAD4 exome

AF:

0.0158

AC:

22904

AN:

1453232

Hom.:

985

Cov.:

AF XY:

0.0151

AC XY:

10892

AN XY:

722746

show subpopulations

Gnomad4 AFR exome

AF:

0.00399

Gnomad4 AMR exome

AF:

0.192

Gnomad4 ASJ exome

AF:

0.0286

Gnomad4 EAS exome

AF:

0.00809

Gnomad4 SAS exome

AF:

0.0124

Gnomad4 FIN exome

AF:

0.00395

Gnomad4 NFE exome

AF:

0.00991

Gnomad4 OTH exome

AF:

0.0172

GnomAD4 genome

AF:

0.0219

AC:

3337

AN:

152278

Hom.:

212

Cov.:

AF XY:

0.0237

AC XY:

1765

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00491

Gnomad4 AMR

AF:

0.135

Gnomad4 ASJ

AF:

0.0354

Gnomad4 EAS

AF:

0.0124

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0119

Hom.:

Bravo

AF:

0.0313

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0114

AC:

ExAC

AF:

0.0284

AC:

3446

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 11, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Adams-Oliver syndrome 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

T;.;T;.

Eigen

Benign

0.046

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

.;.;D;D

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.1

L;.;L;.

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.2

D;D;.;.

REVEL

Benign

0.12

Sift

Uncertain

0.0040

D;T;.;.

Sift4G

Uncertain

0.029

D;D;D;D

Polyphen

0.084

B;B;B;B

Vest4

0.12

MPC

0.19

ClinPred

0.046

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.26

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.76

dbscSNV1_RF

Benign

0.61

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

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