rs387906655

chr6-29659628-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_206809.4(MOG):c.398C>G(p.Ser133Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOG NM_206809.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.236

Genes affected

MOG (HGNC:7197): (myelin oligodendrocyte glycoprotein) The product of this gene is a membrane protein expressed on the oligodendrocyte cell surface and the outermost surface of myelin sheaths. Due to this localization, it is a primary target antigen involved in immune-mediated demyelination. This protein may be involved in completion and maintenance of the myelin sheath and in cell-cell communication. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-29659628-C-G is Pathogenic according to our data. Variant chr6-29659628-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 29798.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null. Variant chr6-29659628-C-G is described in UniProt as null.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOG	NM_206809.4	c.398C>G	p.Ser133Cys	missense_variant	2/8	ENST00000376917.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOG	ENST00000376917.8	c.398C>G	p.Ser133Cys	missense_variant	2/8	1	NM_206809.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Narcolepsy 7 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 09, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
Cadd	Uncertain	26
Dann	Uncertain	0.98
DEOGEN2	Uncertain	0.47	T;.;.;T;.;.;.;.;.
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.24	N
LIST_S2	Uncertain	0.88	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.7	M;M;M;.;M;M;M;M;M
MutationTaster	Benign	0.53	D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.5	D;D;D;N;D;D;D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.012	D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.050	T;D;T;T;T;D;T;T;T
Polyphen		1.0	D;.;D;D;.;D;D;D;D
Vest4		0.67
MutPred		0.46		Loss of disorder (P = 0.0024);Loss of disorder (P = 0.0024);Loss of disorder (P = 0.0024);Loss of disorder (P = 0.0024);Loss of disorder (P = 0.0024);Loss of disorder (P = 0.0024);Loss of disorder (P = 0.0024);Loss of disorder (P = 0.0024);Loss of disorder (P = 0.0024);
MVP		0.83
MPC		0.81
ClinPred		0.91	D
GERP RS		4.8
Varity_R		0.45
gMVP		0.50

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: rs387906655; hg19: chr6-29627405;