3-68977435-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001278689.2(EOGT):c.*183A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 573,144 control chromosomes in the GnomAD database, including 382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (290 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (92 hom.)
• Consequence: EOGT NM_001278689.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.608

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-68977435-T-C is Benign according to our data. Variant chr3-68977435-T-C is described in ClinVar as [Benign]. Clinvar id is 1296435.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EOGT	NM_001278689.2	c.*183A>G		3_prime_UTR_variant	18/18	ENST00000383701.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EOGT	ENST00000383701.8	c.*183A>G		3_prime_UTR_variant	18/18	1	NM_001278689.2	P1
EOGT	ENST00000295571.9	c.*183A>G		3_prime_UTR_variant	15/15	1
EOGT	ENST00000496647.5	n.1421A>G		non_coding_transcript_exon_variant	9/9	2
EOGT	ENST00000403140.6	c.*935A>G		3_prime_UTR_variant, NMD_transcript_variant	16/16	2

Frequencies

GnomAD3 genomes AF: 0.0354 AC: 5382 AN: 152108 Hom.: 291 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0353

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.00569 AC: 2396 AN: 420930 Hom.: 92 Cov.: 6 AF XY: 0.00504 AC XY: 1102 AN XY: 218548

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.00972

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0286

Gnomad4 SAS exome AF: 0.00220

Gnomad4 FIN exome AF: 0.000312

Gnomad4 NFE exome AF: 0.000498

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.0355 AC: 5398 AN: 152214 Hom.: 290 Cov.: 32 AF XY: 0.0342 AC XY: 2542 AN XY: 74426

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0354

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.000472

Gnomad4 NFE AF: 0.000676

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0261 Hom.: 25

Bravo AF: 0.0420

Asia WGS AF: 0.0200 AC: 71 AN: 3478

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

Apr 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.1
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs72922929; hg19: chr3-69026586;