rs13405869

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006302.3(MOGS):c.2032C>T(p.Arg678Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00437 in 1,614,170 control chromosomes in the GnomAD database, including 275 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R678L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.023 ( 148 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 127 hom. )

Consequence

MOGS
NM_006302.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.284

Publications

8 publications found

Variant links:

Genes affected

MOGS (HGNC:24862): (mannosyl-oligosaccharide glucosidase) This gene encodes the first enzyme in the N-linked oligosaccharide processing pathway. The enzyme cleaves the distal alpha-1,2-linked glucose residue from the Glc(3)-Man(9)-GlcNAc(2) oligosaccharide precursor. This protein is located in the lumen of the endoplasmic reticulum. Defects in this gene are a cause of type IIb congenital disorder of glycosylation (CDGIIb). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

MOGS Gene-Disease associations (from GenCC):

MOGS-congenital disorder of glycosylation
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen

MOGS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004419416).

BP6

Variant 2-74461757-G-A is Benign according to our data. Variant chr2-74461757-G-A is described in ClinVar as Benign. ClinVar VariationId is 337105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006302.3. 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
	MOGS	NM_006302.3	MANE Select	c.2032C>T	p.Arg678Trp	missense	Exon 4 of 4	NP_006293.2	A0A384MDR6
	MOGS	NM_001146158.2		c.1714C>T	p.Arg572Trp	missense	Exon 5 of 5	NP_001139630.1	Q13724-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MOGS	ENST00000448666.7	TSL:1 MANE Select	c.2032C>T	p.Arg678Trp	missense	Exon 4 of 4	ENSP00000410992.3	Q13724-1
MOGS	ENST00000452063.7	TSL:1	c.1714C>T	p.Arg572Trp	missense	Exon 5 of 5	ENSP00000388201.2	Q13724-2
MOGS	ENST00000649854.1		c.1663C>T	p.Arg555Trp	missense	Exon 3 of 3	ENSP00000496797.1	A0A3B3IRK6

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3516

AN:

152176

Hom.:

148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0801

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00903

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00587

AC:

1464

AN:

249522

AF XY:

0.00425

show subpopulations

Gnomad AFR exome

AF:

0.0842

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000283

Gnomad OTH exome

AF:

0.00248

GnomAD4 exome

AF:

0.00241

AC:

3523

AN:

1461876

Hom.:

127

Cov.:

AF XY:

0.00204

AC XY:

1483

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0832

AC:

2787

AN:

33480

American (AMR)

AF:

0.00394

AC:

176

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000536

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000162

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000217

AC:

241

AN:

1112008

Other (OTH)

AF:

0.00459

AC:

277

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

254

508

761

1015

1269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0232

AC:

3527

AN:

152294

Hom.:

148

Cov.:

AF XY:

0.0214

AC XY:

1594

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0801

AC:

3328

AN:

41548

American (AMR)

AF:

0.00902

AC:

138

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000621

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68032

Other (OTH)

AF:

0.0151

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

175

349

524

698

873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00818

Hom.:

200

Bravo

AF:

0.0263

ESP6500AA

AF:

0.0779

AC:

309

ESP6500EA

AF:

0.000362

AC:

ExAC

AF:

0.00708

AC:

856

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

MOGS-congenital disorder of glycosylation (2)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.034

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.28

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.20

Sift

Uncertain

0.026

Sift4G

Uncertain

0.014

Polyphen

1.0

Vest4

0.38

MVP

0.47

MPC

0.76

ClinPred

0.043

GERP RS

-0.26

Varity_R

0.12

gMVP

0.76

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over