3-68977324-CA-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001278689.2(EOGT):​c.*293delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (2 hom., cov: 31)
  • Exomes 𝑓: 0.21 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EOGT NM_001278689.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -2 ACMG points.

• BP6: Variant 3-68977324-CA-C is Benign according to our data. Variant chr3-68977324-CA-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1213680.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Frequencies

GnomAD3 genomes AF: 0.00488 AC: 583 AN: 119586 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00735

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00337

Gnomad ASJ AF: 0.00252

Gnomad EAS AF: 0.000711

Gnomad SAS AF: 0.000269

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.00315

Gnomad OTH AF: 0.00447

GnomAD4 exome AF: 0.213 AC: 13066 AN: 61356 Hom.: 0 Cov.: 0 AF XY: 0.212 AC XY: 6954 AN XY: 32806

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

African (AFR) AF: 0.122 AC: 96 AN: 786

American (AMR) AF: 0.208 AC: 157 AN: 756

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 323 AN: 1676

East Asian (EAS) AF: 0.172 AC: 228 AN: 1326

South Asian (SAS) AF: 0.217 AC: 1881 AN: 8660

European-Finnish (FIN) AF: 0.220 AC: 777 AN: 3536

Middle Eastern (MID) AF: 0.178 AC: 51 AN: 286

European-Non Finnish (NFE) AF: 0.215 AC: 8788 AN: 40782

Other (OTH) AF: 0.216 AC: 765 AN: 3548

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00495 AC: 592 AN: 119630 Hom.: 2 Cov.: 31 AF XY: 0.00524 AC XY: 299 AN XY: 57098

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

African (AFR) AF: 0.00752 AC: 271 AN: 36022

American (AMR) AF: 0.00345 AC: 39 AN: 11292

Ashkenazi Jewish (ASJ) AF: 0.00252 AC: 7 AN: 2782

East Asian (EAS) AF: 0.000713 AC: 3 AN: 4208

South Asian (SAS) AF: 0.000271 AC: 1 AN: 3694

European-Finnish (FIN) AF: 0.0157 AC: 95 AN: 6036

Middle Eastern (MID) AF: 0.00459 AC: 1 AN: 218

European-Non Finnish (NFE) AF: 0.00315 AC: 167 AN: 53090

Other (OTH) AF: 0.00506 AC: 8 AN: 1580

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely 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		-0.60
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;