3-68977324-CAAAAA-CAAA

Variant names:

• chr3-68977324-CAA-C
• rs59164738
• NM_001278689.2:c.*292_*293delTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001278689.2(EOGT):​c.*292_*293delTT 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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Adams-Oliver syndrome 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Adams-Oliver syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278689.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EOGT	NM_001278689.2	MANE Select	c.*292_*293delTT		3_prime_UTR	Exon 18 of 18	NP_001265618.1	Q5NDL2-1
	EOGT	NM_173654.3		c.*292_*293delTT		3_prime_UTR	Exon 15 of 15	NP_775925.1	Q5NDL2-3
	EOGT	NR_103826.2		n.2131_2132delTT		non_coding_transcript_exon	Exon 16 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EOGT	ENST00000383701.8	TSL:1 MANE Select	c.*292_*293delTT		3_prime_UTR	Exon 18 of 18	ENSP00000373206.3	Q5NDL2-1
	EOGT	ENST00000295571.9	TSL:1	c.*292_*293delTT		3_prime_UTR	Exon 15 of 15	ENSP00000295571.5	Q5NDL2-3
	EOGT	ENST00000403140.6	TSL:2	n.*1044_*1045delTT		non_coding_transcript_exon	Exon 16 of 16	ENSP00000384124.2	F5H225

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.275 AC: 218 AN: 794

American (AMR) AF: 0.0545 AC: 41 AN: 752

Ashkenazi Jewish (ASJ) AF: 0.0354 AC: 59 AN: 1666

East Asian (EAS) AF: 0.0679 AC: 90 AN: 1326

South Asian (SAS) AF: 0.0398 AC: 341 AN: 8568

European-Finnish (FIN) AF: 0.0262 AC: 92 AN: 3510

Middle Eastern (MID) AF: 0.0571 AC: 16 AN: 280

European-Non Finnish (NFE) AF: 0.0396 AC: 1597 AN: 40336

Other (OTH) AF: 0.0496 AC: 176 AN: 3546

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.380 AC: 13665 AN: 35968

American (AMR) AF: 0.0707 AC: 799 AN: 11294

Ashkenazi Jewish (ASJ) AF: 0.00108 AC: 3 AN: 2790

East Asian (EAS) AF: 0.0939 AC: 395 AN: 4206

South Asian (SAS) AF: 0.0206 AC: 76 AN: 3694

European-Finnish (FIN) AF: 0.0108 AC: 65 AN: 6046

Middle Eastern (MID) AF: 0.0275 AC: 6 AN: 218

European-Non Finnish (NFE) AF: 0.0172 AC: 915 AN: 53246

Other (OTH) AF: 0.118 AC: 186 AN: 1582

Alfa AF: 0.000985 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.32
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs59164738; hg19: chr3-69026475;