rs1558564232

Variant names:

• chr2-74461313-T-A
• rs1558564232
• NM_006302.3:c.2476A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-74461313-T-A
• chr2-74461313-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006302.3(MOGS):​c.2476A>T​(p.Thr826Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MOGS NM_006302.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.73

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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.2476A>T	p.Thr826Ser	missense_variant	Exon 4 of 4	ENST00000448666.7	NP_006293.2
MOGS	NM_001146158.2	c.2158A>T	p.Thr720Ser	missense_variant	Exon 5 of 5		NP_001139630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOGS	ENST00000448666.7	c.2476A>T	p.Thr826Ser	missense_variant	Exon 4 of 4	1	NM_006302.3	ENSP00000410992.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.016	T;T;.;.;.
Eigen	Benign	-0.025
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	.;D;.;D;D
M_CAP	Benign	0.0034	T
MetaRNN	Uncertain	0.58	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.18	N;N;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.030	.;N;.;.;N
REVEL	Benign	0.12
Sift	Benign	0.77	.;T;.;.;T
Sift4G	Benign	1.0	.;T;.;.;T
Polyphen		0.45	B;B;.;.;.
Vest4		0.17, 0.17
MutPred		0.91		Gain of catalytic residue at T826 (P = 0.2729);Gain of catalytic residue at T826 (P = 0.2729);.;.;.;
MVP		0.70
MPC		0.39
ClinPred		0.44	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.044
gMVP		0.78

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

Other links and lift over

dbSNP: rs1558564232; hg19: chr2-74688440;