Variant rs147327086 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001278689.2(EOGT):c.783C>T(p.His261=) 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

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 Benign. Variant got -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EOGT	NM_001278689.2 linkuse as main transcript	c.783C>T	p.His261=	synonymous_variant	10/18	ENST00000383701.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EOGT	ENST00000383701.8 linkuse as main transcript	c.783C>T	p.His261=	synonymous_variant	10/18	1	NM_001278689.2	P1	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

GnomAD3 exomes

AF:

0.00463

AC:

1122

AN:

242154

Hom.:

AF XY:

0.00556

AC XY:

728

AN XY:

131034

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 SAS exome

AF:

0.0136

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

Gnomad4 AFR exome

AF:

0.000879

Gnomad4 AMR exome

AF:

0.00286

Gnomad4 ASJ exome

AF:

0.00146

Gnomad4 EAS exome

AF:

0.000407

Gnomad4 SAS exome

AF:

0.0141

Gnomad4 FIN exome

AF:

0.00146

Gnomad4 NFE exome

AF:

0.00564

Gnomad4 OTH exome

AF:

0.00409

GnomAD4 genome

AF:

0.00379

AC:

577

AN:

152278

Hom.:

Cov.:

AF XY:

0.00377

AC XY:

281

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00953

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00585

Gnomad4 OTH

AF:

0.00284

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 11, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jul 08, 2016	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	EOGT: BP4, BP7, BS1, BS2 -
Likely 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 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.9

DANN

Benign

0.78

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

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