rs1553380245

Variant names:

• chr2-74464937-T-G
• rs1553380245
• NM_006302.3:c.311A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-74464937-T-G
• chr2-74464937-T-C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_006302.3(MOGS):​c.311A>C​(p.Tyr104Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MOGS NM_006302.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 4.25
• Publications: 0 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: 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, 0.962

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.311A>C	p.Tyr104Ser	missense	Exon 1 of 4	NP_006293.2	A0A384MDR6
	MOGS	NM_001146158.2		c.-8A>C		5_prime_UTR	Exon 2 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.311A>C	p.Tyr104Ser	missense	Exon 1 of 4	ENSP00000410992.3	Q13724-1
	MOGS	ENST00000452063.7	TSL:1	c.-8A>C		5_prime_UTR	Exon 2 of 5	ENSP00000388201.2	Q13724-2
	MOGS	ENST00000690565.1		c.311A>C	p.Tyr104Ser	missense	Exon 1 of 5	ENSP00000510501.1	A0A8I5KTK5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	MOGS-congenital disorder of glycosylation (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		4.2
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-8.3	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.019	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.86		Gain of disorder (P = 0.0081)
MVP		0.84
MPC		1.0
ClinPred		1.0	D
GERP RS		3.6
PromoterAI		-0.017	Neutral
Varity_R		0.97
gMVP		0.98
Mutation Taster		=36/64	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1553380245; hg19: chr2-74692064;