NM_001278689.2:c.562A>G

Variant names:

• chr3-69004436-T-C
• NM_001278689.2:c.562A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001278689.2(EOGT):​c.562A>G​(p.Lys188Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: EOGT NM_001278689.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.862

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12548506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EOGT	NM_001278689.2	c.562A>G	p.Lys188Glu	missense_variant	Exon 8 of 18	ENST00000383701.8	NP_001265618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EOGT	ENST00000383701.8	c.562A>G	p.Lys188Glu	missense_variant	Exon 8 of 18	1	NM_001278689.2	ENSP00000373206.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461836 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.23
DEOGEN2	Benign	0.0095	T;.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.54	.;.;T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.3	L;L;L;L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.57	N;N;.;.
REVEL	Benign	0.064
Sift	Benign	0.34	T;T;.;.
Sift4G	Benign	0.71	T;T;T;T
Polyphen		0.0030	B;B;B;B
Vest4		0.23
MutPred		0.57		Loss of methylation at K188 (P = 0.0127);Loss of methylation at K188 (P = 0.0127);Loss of methylation at K188 (P = 0.0127);Loss of methylation at K188 (P = 0.0127);
MVP		0.11
MPC		0.20
ClinPred		0.045	T
GERP RS		-0.90
Varity_R		0.036
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-69053587;