rs116711473

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 8P and 9B. PVS1BP6BS1BS2

The NM_001278689.2(EOGT):c.562A>T(p.Lys188*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,614,144 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0084 ( 19 hom., cov: 31)

Exomes 𝑓: 0.00099 ( 21 hom. )

Consequence

EOGT
NM_001278689.2 stop_gained

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 0.862

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 Likely_benign. Variant got -1 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

BP6

Variant 3-69004436-T-A is Benign according to our data. Variant chr3-69004436-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 445341.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=2, Uncertain_significance=1}. Variant chr3-69004436-T-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00835 (1272/152322) while in subpopulation AFR AF= 0.0284 (1182/41570). AF 95% confidence interval is 0.0271. There are 19 homozygotes in gnomad4. There are 614 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EOGT	NM_001278689.2 link	c.562A>T	p.Lys188*	stop_gained	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.562A>T	p.Lys188*	stop_gained	Exon 8 of 18	1	NM_001278689.2	ENSP00000373206.3		Q5NDL2-1

Frequencies

GnomAD3 genomes

AF:

0.00836

AC:

1272

AN:

152204

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

GnomAD3 exomes

AF:

0.00230

AC:

578

AN:

251444

Hom.:

AF XY:

0.00180

AC XY:

245

AN XY:

135898

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 SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000814

GnomAD4 exome

AF:

0.000992

AC:

1450

AN:

1461822

Hom.:

Cov.:

AF XY:

0.000949

AC XY:

690

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0299

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00161

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00835

AC:

1272

AN:

152322

Hom.:

Cov.:

AF XY:

0.00824

AC XY:

614

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0284

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.00954

ESP6500AA

AF:

0.0229

AC:

101

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: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EOGT: BS1, BS2 -

Oct 02, 2020

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31724708, 28600779, 30290772) -

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

- -

Adams-Oliver syndrome 4

Benign:1

Dec 31, 2019

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_addAF

Benign

-0.098

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Benign

0.90

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.62

FATHMM_MKL

Uncertain

0.86

Vest4

0.45

GERP RS

-0.90

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

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