dbSNP rs777633686: MOG:p.Leu112Val (chr6-29659564-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L112F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

MOG
NM_206809.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.32

Publications

1 publications found

Variant links:

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)

MOG links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.879

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MOG	NM_206809.4	MANE Select	c.334C>G	p.Leu112Val	missense	Exon 2 of 8	NP_996532.2	Q16653-1
MOG	NM_001363610.2		c.334C>G	p.Leu112Val	missense	Exon 2 of 7	NP_001350539.1	Q16653-13
MOG	NM_002433.5		c.334C>G	p.Leu112Val	missense	Exon 2 of 8	NP_002424.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MOG	ENST00000376917.8	TSL:1 MANE Select	c.334C>G	p.Leu112Val	missense	Exon 2 of 8	ENSP00000366115.3	Q16653-1
MOG	ENST00000376894.8	TSL:1	c.334C>G	p.Leu112Val	missense	Exon 2 of 7	ENSP00000366091.4	Q16653-13
MOG	ENST00000376898.7	TSL:1	c.334C>G	p.Leu112Val	missense	Exon 2 of 8	ENSP00000366095.3	Q16653-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000406

AC:

AN:

246608

AF XY:

0.00000744

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000846

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.056

MetaRNN

Pathogenic

0.88

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.8

PhyloP100

2.3

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.91

REVEL

Uncertain

0.38

Sift

Benign

0.53

Sift4G

Benign

0.065

Polyphen

1.0

Vest4

0.79

MutPred

0.78

Gain of MoRF binding (P = 0.0951)

MVP

0.76

MPC

0.87

ClinPred

0.60

GERP RS

4.8

Varity_R

0.26

gMVP

0.70

Mutation Taster

=72/28

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over