3-68977324-CAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001278689.2(EOGT):c.*292_*293del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 180,530 control chromosomes in the GnomAD database, including 2,403 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (2384 hom., cov: 30)
  • Exomes 𝑓: 0.043 (19 hom.)
• Consequence: EOGT NM_001278689.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.317

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 -10 ACMG points.

• BP6: Variant 3-68977324-CAA-C is Benign according to our data. Variant chr3-68977324-CAA-C is described in ClinVar as [Benign]. Clinvar id is 1247777.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EOGT	NM_001278689.2	c.*292_*293del		3_prime_UTR_variant	18/18	ENST00000383701.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EOGT	ENST00000383701.8	c.*292_*293del		3_prime_UTR_variant	18/18	1	NM_001278689.2	P1
EOGT	ENST00000295571.9	c.*292_*293del		3_prime_UTR_variant	15/15	1
EOGT	ENST00000496647.5	n.1530_1531del		non_coding_transcript_exon_variant	9/9	2
EOGT	ENST00000403140.6	c.*1044_*1045del		3_prime_UTR_variant, NMD_transcript_variant	16/16	2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 16080 AN: 119710 Hom.: 2377 Cov.: 30

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.00108

Gnomad EAS AF: 0.0936

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.0378

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.0433 AC: 2630 AN: 60778 Hom.: 19 AF XY: 0.0419 AC XY: 1361 AN XY: 32490

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.0545

Gnomad4 ASJ exome AF: 0.0354

Gnomad4 EAS exome AF: 0.0679

Gnomad4 SAS exome AF: 0.0398

Gnomad4 FIN exome AF: 0.0262

Gnomad4 NFE exome AF: 0.0396

Gnomad4 OTH exome AF: 0.0496

GnomAD4 genome AF: 0.135 AC: 16110 AN: 119752 Hom.: 2384 Cov.: 30 AF XY: 0.134 AC XY: 7668 AN XY: 57158

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.0707

Gnomad4 ASJ AF: 0.00108

Gnomad4 EAS AF: 0.0939

Gnomad4 SAS AF: 0.0206

Gnomad4 FIN AF: 0.0108

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.118

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs59164738; hg19: chr3-69026475;