Variant chr2-74465145-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006302.3(MOGS):c.103G>C(p.Gly35Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,379,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G35S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

MOGS
NM_006302.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.271

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 links:

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ACMG classification

Classification made for transcript

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=0.089232385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOGS	NM_006302.3 linkuse as main transcript	c.103G>C	p.Gly35Arg	missense_variant	1/4	ENST00000448666.7
MOGS	NM_001146158.2 linkuse as main transcript	c.-58-158G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOGS	ENST00000448666.7 linkuse as main transcript	c.103G>C	p.Gly35Arg	missense_variant	1/4	1	NM_006302.3	P1	Q13724-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

125692

Hom.:

AF XY:

0.0000145

AC XY:

AN XY:

69114

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000833

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000218

AC:

AN:

1379266

Hom.:

Cov.:

AF XY:

0.00000294

AC XY:

AN XY:

680602

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000848

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0029

T;T;T;.;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.56

.;T;T;T;T

M_CAP

Benign

0.061

MetaRNN

Benign

0.089

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.;.;.

MutationTaster

Benign

0.56

D;N;N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.23

.;N;N;.;.

REVEL

Benign

0.054

Sift

Uncertain

0.016

.;D;D;.;.

Sift4G

Benign

0.56

.;T;T;.;.

Polyphen

0.0030

B;B;.;.;.

Vest4

0.32, 0.27

MutPred

0.30

Gain of methylation at G35 (P = 0.0056);Gain of methylation at G35 (P = 0.0056);Gain of methylation at G35 (P = 0.0056);Gain of methylation at G35 (P = 0.0056);Gain of methylation at G35 (P = 0.0056);

MVP

0.24

MPC

0.36

ClinPred

0.065

GERP RS

1.8

Varity_R

0.042

gMVP

0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over