NM_206809.4:c.208C>A

Variant names:

• chr6-29659438-C-A
• rs749783831
• NM_206809.4:c.208C>A

Variant summary

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

The NM_206809.4(MOG):​c.208C>A​(p.Arg70Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. R70C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MOG NM_206809.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 0 publications found

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]

MOG Gene-Disease associations (from GenCC):

• narcolepsy 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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, 0.946

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206809.4. 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
	MOG	NM_206809.4	MANE Select	c.208C>A	p.Arg70Ser	missense	Exon 2 of 8	NP_996532.2	Q16653-1
	MOG	NM_001363610.2		c.208C>A	p.Arg70Ser	missense	Exon 2 of 7	NP_001350539.1	Q16653-13
	MOG	NM_002433.5		c.208C>A	p.Arg70Ser	missense	Exon 2 of 8	NP_002424.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOG	ENST00000376917.8	TSL:1 MANE Select	c.208C>A	p.Arg70Ser	missense	Exon 2 of 8	ENSP00000366115.3	Q16653-1
	MOG	ENST00000376894.8	TSL:1	c.208C>A	p.Arg70Ser	missense	Exon 2 of 7	ENSP00000366091.4	Q16653-13
	MOG	ENST00000376898.7	TSL:1	c.208C>A	p.Arg70Ser	missense	Exon 2 of 8	ENSP00000366095.3	Q16653-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		1.5
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.62
Sift	Benign	0.15	T
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.70		Loss of MoRF binding (P = 0.0386)
MVP		0.87
MPC		0.93
ClinPred		0.97	D
GERP RS		3.9
Varity_R		0.60
gMVP		0.87
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs749783831; hg19: chr6-29627215;