NM_006302.3:c.715G>C

Variant names:

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

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

ACMG classification

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

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

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.715G>C	p.Asp239His	missense	Exon 3 of 4	NP_006293.2	A0A384MDR6
	MOGS	NM_001146158.2		c.397G>C	p.Asp133His	missense	Exon 4 of 5	NP_001139630.1	Q13724-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOGS	ENST00000448666.7	TSL:1 MANE Select	c.715G>C	p.Asp239His	missense	Exon 3 of 4	ENSP00000410992.3	Q13724-1
	MOGS	ENST00000452063.7	TSL:1	c.397G>C	p.Asp133His	missense	Exon 4 of 5	ENSP00000388201.2	Q13724-2
	MOGS	ENST00000690565.1		c.715G>C	p.Asp239His	missense	Exon 3 of 5	ENSP00000510501.1	A0A8I5KTK5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.1
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.20
Sift	Benign	0.080	T
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.18
MutPred		0.40		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;