rs147327086

chr3-68998059-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.374

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]

ACMG classification

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 GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EOGT	NM_001278689.2	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	c.783C>T	p.His261=	synonymous_variant	10/18	1	NM_001278689.2	P1

Frequencies

GnomAD3 genomes AF: 0.00379 AC: 576 AN: 152160 Hom.: 3 Cov.: 33

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.: 6 AF XY: 0.00556 AC XY: 728 AN XY: 131034

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.: 39 Cov.: 28 AF XY: 0.00594 AC XY: 4287 AN XY: 721126

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.: 3 Cov.: 33 AF XY: 0.00377 AC XY: 281 AN XY: 74466

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.: 0

Bravo AF: 0.00379

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

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 -

Adams-Oliver syndrome 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

Other links and lift over

dbSNP: rs147327086; hg19: chr3-69047210; COSMIC: COSV55153556;