3-68977747-C-G

Variant names:

• chr3-68977747-C-G
• NM_001278689.2:c.1455G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001278689.2(EOGT):​c.1455G>C​(p.Leu485Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EOGT NM_001278689.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0260
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 3-68977747-C-G is Benign according to our data. Variant chr3-68977747-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2799428.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.026 with no splicing effect.

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.1455G>C	p.Leu485Leu	synonymous	Exon 18 of 18	NP_001265618.1	Q5NDL2-1
	EOGT	NM_173654.3		c.1203G>C	p.Leu401Leu	synonymous	Exon 15 of 15	NP_775925.1	Q5NDL2-3
	EOGT	NR_103826.2		n.1710G>C		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.1455G>C	p.Leu485Leu	synonymous	Exon 18 of 18	ENSP00000373206.3	Q5NDL2-1
	EOGT	ENST00000295571.9	TSL:1	c.1203G>C	p.Leu401Leu	synonymous	Exon 15 of 15	ENSP00000295571.5	Q5NDL2-3
	EOGT	ENST00000894422.1		c.1455G>C	p.Leu485Leu	synonymous	Exon 17 of 17	ENSP00000564481.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Adams-Oliver syndrome 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	5.8
DANN	Benign	0.68
PhyloP100		0.026

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

hg19: chr3-69026898;