rs1063588

Variant names:

• chr2-74463251-C-G
• rs1063588
• NM_006302.3:c.715G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-74463251-C-G
• chr2-74463251-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006302.3(MOGS):​c.715G>C​(p.Asp239His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. D239N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOGS NM_006302.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 68 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOGS	NM_006302.3	c.715G>C	p.Asp239His	missense_variant	Exon 3 of 4	ENST00000448666.7	NP_006293.2
MOGS	NM_001146158.2	c.397G>C	p.Asp133His	missense_variant	Exon 4 of 5		NP_001139630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOGS	ENST00000448666.7	c.715G>C	p.Asp239His	missense_variant	Exon 3 of 4	1	NM_006302.3	ENSP00000410992.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;T;.;.;.;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.72	.;T;T;T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.62	D;D;D;D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.4	L;L;.;.;.;.
PhyloP100		1.1
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.0	.;N;.;N;.;N
REVEL	Benign	0.20
Sift	Benign	0.080	.;T;.;T;.;T
Sift4G	Benign	0.16	.;T;.;T;.;T
Polyphen		1.0	D;D;.;.;.;.
Vest4		0.18, 0.21
MutPred		0.40		Gain of disorder (P = 0.0844);Gain of disorder (P = 0.0844);Gain of disorder (P = 0.0844);.;.;.;
MVP		0.71
MPC		0.91
ClinPred		0.89	D
GERP RS		4.8
Varity_R		0.32
gMVP		0.67
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs1063588; hg19: chr2-74690378;