chr3-68977324-CAAA-C

Variant names:

• chr3-68977324-CAAA-C
• rs59164738
• NM_001278689.2:c.*291_*293delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001278689.2(EOGT):​c.*291_*293delTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000743 in 182,998 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000058 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0020 (0 hom.)
• Consequence: EOGT NM_001278689.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.*291_*293delTTT		3_prime_UTR	Exon 18 of 18	NP_001265618.1	Q5NDL2-1
	EOGT	NM_173654.3		c.*291_*293delTTT		3_prime_UTR	Exon 15 of 15	NP_775925.1	Q5NDL2-3
	EOGT	NR_103826.2		n.2130_2132delTTT		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.*291_*293delTTT		3_prime_UTR	Exon 18 of 18	ENSP00000373206.3	Q5NDL2-1
	EOGT	ENST00000295571.9	TSL:1	c.*291_*293delTTT		3_prime_UTR	Exon 15 of 15	ENSP00000295571.5	Q5NDL2-3
	EOGT	ENST00000403140.6	TSL:2	n.*1043_*1045delTTT		non_coding_transcript_exon	Exon 16 of 16	ENSP00000384124.2	F5H225

Frequencies

GnomAD3 genomes AF: 0.0000584 AC: 7 AN: 119930 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000885

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00205 AC: 129 AN: 63026 Hom.: 0 AF XY: 0.00208 AC XY: 70 AN XY: 33708

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

African (AFR) AF: 0.0125 AC: 10 AN: 802

American (AMR) AF: 0.00 AC: 0 AN: 768

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 2 AN: 1722

East Asian (EAS) AF: 0.00368 AC: 5 AN: 1360

South Asian (SAS) AF: 0.00248 AC: 22 AN: 8884

European-Finnish (FIN) AF: 0.00218 AC: 8 AN: 3670

Middle Eastern (MID) AF: 0.00699 AC: 2 AN: 286

European-Non Finnish (NFE) AF: 0.00174 AC: 73 AN: 41904

Other (OTH) AF: 0.00193 AC: 7 AN: 3630

⚠️ 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: 0.0000583 AC: 7 AN: 119972 Hom.: 0 Cov.: 30 AF XY: 0.0000524 AC XY: 3 AN XY: 57278

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

African (AFR) AF: 0.000167 AC: 6 AN: 36034

American (AMR) AF: 0.0000884 AC: 1 AN: 11316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2790

East Asian (EAS) AF: 0.00 AC: 0 AN: 4210

South Asian (SAS) AF: 0.00 AC: 0 AN: 3694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53310

Other (OTH) AF: 0.00 AC: 0 AN: 1584

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0500038), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.90

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;