6-29659438-C-A

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. Variant got 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.

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

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.946

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOG	NM_206809.4	c.208C>A	p.Arg70Ser	missense_variant	Exon 2 of 8	ENST00000376917.8	NP_996532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOG	ENST00000376917.8	c.208C>A	p.Arg70Ser	missense_variant	Exon 2 of 8	1	NM_206809.4	ENSP00000366115.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;.;T;.;.;.;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.95	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	3.4	M;M;M;.;M;M;M;M;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-4.1	D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.62
Sift	Benign	0.15	T;T;T;T;D;T;T;T;D
Sift4G	Uncertain	0.0090	D;D;D;D;D;D;D;D;D
Polyphen		1.0	D;.;D;D;.;D;D;D;D
Vest4		0.88
MutPred		0.70		Loss of MoRF binding (P = 0.0386);Loss of MoRF binding (P = 0.0386);Loss of MoRF binding (P = 0.0386);Loss of MoRF binding (P = 0.0386);Loss of MoRF binding (P = 0.0386);Loss of MoRF binding (P = 0.0386);Loss of MoRF binding (P = 0.0386);Loss of MoRF binding (P = 0.0386);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-29627215;