3-68977324-CAAAAA-CAAAAAA

Variant names:

• chr3-68977324-C-CA
• rs59164738
• NM_001278689.2:c.*293dupT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001278689.2(EOGT):​c.*293dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 181,982 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 31)
  • Exomes 𝑓: 0.087 (0 hom.)
• Consequence: EOGT NM_001278689.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603
• 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00192 (230/119832) while in subpopulation EAS AF = 0.00594 (25/4208). AF 95% confidence interval is 0.00413. There are 1 homozygotes in GnomAd4. There are 125 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

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.*293dupT		3_prime_UTR	Exon 18 of 18	NP_001265618.1	Q5NDL2-1
	EOGT	NM_173654.3		c.*293dupT		3_prime_UTR	Exon 15 of 15	NP_775925.1	Q5NDL2-3
	EOGT	NR_103826.2		n.2132dupT		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.*293dupT		3_prime_UTR	Exon 18 of 18	ENSP00000373206.3	Q5NDL2-1
	EOGT	ENST00000295571.9	TSL:1	c.*293dupT		3_prime_UTR	Exon 15 of 15	ENSP00000295571.5	Q5NDL2-3
	EOGT	ENST00000403140.6	TSL:2	n.*1045dupT		non_coding_transcript_exon	Exon 16 of 16	ENSP00000384124.2	F5H225

Frequencies

GnomAD3 genomes AF: 0.00193 AC: 231 AN: 119786 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00310

Gnomad ASJ AF: 0.00467

Gnomad EAS AF: 0.00592

Gnomad SAS AF: 0.00188

Gnomad FIN AF: 0.00445

Gnomad MID AF: 0.0126

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.0874 AC: 5431 AN: 62150 Hom.: 0 Cov.: 0 AF XY: 0.0900 AC XY: 2987 AN XY: 33204

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

African (AFR) AF: 0.0512 AC: 41 AN: 800

American (AMR) AF: 0.0669 AC: 51 AN: 762

Ashkenazi Jewish (ASJ) AF: 0.0943 AC: 159 AN: 1686

East Asian (EAS) AF: 0.0815 AC: 109 AN: 1338

South Asian (SAS) AF: 0.0895 AC: 783 AN: 8746

European-Finnish (FIN) AF: 0.0803 AC: 291 AN: 3626

Middle Eastern (MID) AF: 0.0951 AC: 27 AN: 284

European-Non Finnish (NFE) AF: 0.0887 AC: 3666 AN: 41312

Other (OTH) AF: 0.0845 AC: 304 AN: 3596

⚠️ 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: 0.00192 AC: 230 AN: 119832 Hom.: 1 Cov.: 31 AF XY: 0.00218 AC XY: 125 AN XY: 57224

African (AFR) AF: 0.000999 AC: 36 AN: 36024

American (AMR) AF: 0.00310 AC: 35 AN: 11306

Ashkenazi Jewish (ASJ) AF: 0.00467 AC: 13 AN: 2784

East Asian (EAS) AF: 0.00594 AC: 25 AN: 4208

South Asian (SAS) AF: 0.00190 AC: 7 AN: 3690

European-Finnish (FIN) AF: 0.00445 AC: 27 AN: 6074

Middle Eastern (MID) AF: 0.00917 AC: 2 AN: 218

European-Non Finnish (NFE) AF: 0.00154 AC: 82 AN: 53240

Other (OTH) AF: 0.00190 AC: 3 AN: 1582

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.60
Mutation Taster		=99/1	polymorphism

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;