dbSNP rs1553380245: MOGS:c.-8A>G (chr2-74464937-T-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000452063.7(MOGS):c.-8A>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000069 in 1,449,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MOGS
ENST00000452063.7 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.25

Publications

0 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: Ambry Genetics, G2P, Orphanet, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)

MOGS links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOGS	NM_006302.3 link	c.311A>G	p.Tyr104Cys	missense_variant	Exon 1 of 4	ENST00000448666.7	NP_006293.2	Q13724-1A0A384MDR6
MOGS	NM_001146158.2 link	c.-8A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5		NP_001139630.1	Q13724-2Q58F09
MOGS	NM_001146158.2 link	c.-8A>G		5_prime_UTR_variant	Exon 2 of 5		NP_001139630.1	Q13724-2Q58F09

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOGS	ENST00000448666.7 link	c.311A>G	p.Tyr104Cys	missense_variant	Exon 1 of 4	1	NM_006302.3	ENSP00000410992.3		Q13724-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449770

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719662

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33322

American (AMR)

AF:

0.00

AC:

AN:

43182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25840

East Asian (EAS)

AF:

0.00

AC:

AN:

39192

South Asian (SAS)

AF:

0.00

AC:

AN:

84468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105874

Other (OTH)

AF:

0.00

AC:

AN:

59822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T;T;.;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.93

.;D;D;D;D

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.97

D;D;D;D;D

MetaSVM

Uncertain

-0.10

MutationAssessor

Pathogenic

3.5

H;H;.;.;.

PhyloP100

4.2

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-8.3

.;D;D;.;.

REVEL

Uncertain

0.62

Sift

Uncertain

0.0010

.;D;D;.;.

Sift4G

Pathogenic

0.0

.;D;D;.;.

Polyphen

1.0

D;D;.;.;.

Vest4

0.86, 0.92

MutPred

0.89

Loss of phosphorylation at Y104 (P = 0.0149);Loss of phosphorylation at Y104 (P = 0.0149);Loss of phosphorylation at Y104 (P = 0.0149);Loss of phosphorylation at Y104 (P = 0.0149);Loss of phosphorylation at Y104 (P = 0.0149);

MVP

0.85

MPC

0.97

ClinPred

1.0

GERP RS

3.6

PromoterAI

-0.016

Neutral

(source)

Varity_R

0.98

gMVP

0.98

Mutation Taster

=36/64

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over