rs777633686

Variant names:

• chr6-29659564-C-G
• rs777633686
• NM_206809.4:c.334C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-29659564-C-G
• chr6-29659564-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_206809.4(MOG):​c.334C>G​(p.Leu112Val) 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: 2.32

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.879

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOG	NM_206809.4	c.334C>G	p.Leu112Val	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.334C>G	p.Leu112Val	missense_variant	Exon 2 of 8	1	NM_206809.4	ENSP00000366115.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000406 AC: 1 AN: 246608 Hom.: 0 AF XY: 0.00000744 AC XY: 1 AN XY: 134422

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000903

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000846 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;.;.;T;.;.;.;.;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.056	D
MetaRNN	Pathogenic	0.88	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.8	L;L;L;.;L;L;L;L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.91	N;N;N;N;N;N;N;N;N
REVEL	Uncertain	0.38
Sift	Benign	0.53	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.065	T;T;T;T;T;T;T;T;T
Polyphen		1.0	D;.;D;D;.;D;D;D;D
Vest4		0.79
MutPred		0.78		Gain of MoRF binding (P = 0.0951);Gain of MoRF binding (P = 0.0951);Gain of MoRF binding (P = 0.0951);Gain of MoRF binding (P = 0.0951);Gain of MoRF binding (P = 0.0951);Gain of MoRF binding (P = 0.0951);Gain of MoRF binding (P = 0.0951);Gain of MoRF binding (P = 0.0951);Gain of MoRF binding (P = 0.0951);
MVP		0.76
MPC		0.87
ClinPred		0.60	D
GERP RS		4.8
Varity_R		0.26
gMVP		0.70

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: rs777633686; hg19: chr6-29627341;