rs147327086

Variant names:

• chr3-68998059-G-A
• rs147327086
• NM_001278689.2:c.783C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-68998059-G-A
• chr3-68998059-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001278689.2(EOGT):​c.783C>T​(p.His261His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00534 in 1,601,624 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0055 (39 hom.)
• Consequence: EOGT NM_001278689.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.374
• Publications: 6 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 3-68998059-G-A is Benign according to our data. Variant chr3-68998059-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 376918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.374 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00379 (577/152278) while in subpopulation SAS AF = 0.00953 (46/4828). AF 95% confidence interval is 0.00734. There are 3 homozygotes in GnomAd4. There are 281 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,AD gene

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.783C>T	p.His261His	synonymous	Exon 10 of 18	NP_001265618.1	Q5NDL2-1
	EOGT	NM_173654.3		c.783C>T	p.His261His	synonymous	Exon 10 of 15	NP_775925.1	Q5NDL2-3
	EOGT	NR_103826.2		n.1086+6319C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EOGT	ENST00000383701.8	TSL:1 MANE Select	c.783C>T	p.His261His	synonymous	Exon 10 of 18	ENSP00000373206.3	Q5NDL2-1
	EOGT	ENST00000295571.9	TSL:1	c.783C>T	p.His261His	synonymous	Exon 10 of 15	ENSP00000295571.5	Q5NDL2-3
	EOGT	ENST00000894422.1		c.783C>T	p.His261His	synonymous	Exon 9 of 17	ENSP00000564481.1

Frequencies

GnomAD3 genomes AF: 0.00379 AC: 576 AN: 152160 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00585

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00463 AC: 1122 AN: 242154 AF XY: 0.00556

Gnomad AFR exome AF: 0.00101

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00151

Gnomad EAS exome AF: 0.0000562

Gnomad FIN exome AF: 0.00130

Gnomad NFE exome AF: 0.00508

Gnomad OTH exome AF: 0.00546

GnomAD4 exome AF: 0.00551 AC: 7983 AN: 1449346 Hom.: 39 Cov.: 28 AF XY: 0.00594 AC XY: 4287 AN XY: 721126

African (AFR) AF: 0.000879 AC: 29 AN: 32994

American (AMR) AF: 0.00286 AC: 121 AN: 42302

Ashkenazi Jewish (ASJ) AF: 0.00146 AC: 38 AN: 25968

East Asian (EAS) AF: 0.000407 AC: 16 AN: 39276

South Asian (SAS) AF: 0.0141 AC: 1179 AN: 83876

European-Finnish (FIN) AF: 0.00146 AC: 78 AN: 53334

Middle Eastern (MID) AF: 0.00747 AC: 43 AN: 5758

European-Non Finnish (NFE) AF: 0.00564 AC: 6234 AN: 1105890

Other (OTH) AF: 0.00409 AC: 245 AN: 59948

GnomAD4 genome AF: 0.00379 AC: 577 AN: 152278 Hom.: 3 Cov.: 33 AF XY: 0.00377 AC XY: 281 AN XY: 74466

African (AFR) AF: 0.000890 AC: 37 AN: 41558

American (AMR) AF: 0.00301 AC: 46 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00953 AC: 46 AN: 4828

European-Finnish (FIN) AF: 0.00170 AC: 18 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00585 AC: 398 AN: 68018

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00465 Hom.: 0

Bravo AF: 0.00379

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Adams-Oliver syndrome 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.9
DANN	Benign	0.78
PhyloP100		0.37
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs147327086; hg19: chr3-69047210; COSMIC: COSV55153556;