Genetic Variant MOG:p.Pro40Ser (chr6-29659348-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_206809.4(MOG):c.118C>T(p.Pro40Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,674 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MOG
NM_206809.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.12

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOG	NM_206809.4 link	c.118C>T	p.Pro40Ser	missense_variant	Exon 2 of 8	ENST00000376917.8	NP_996532.2	Q16653-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOG	ENST00000376917.8 link	c.118C>T	p.Pro40Ser	missense_variant	Exon 2 of 8	1	NM_206809.4	ENSP00000366115.3		Q16653-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246472

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134340

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000904

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460674

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726638

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000852

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

T;.;.;T;.;.;.;.;.

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.075

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.95

D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.54

D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M;M;.;M;M;M;M;M

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-6.9

D;D;D;D;D;D;D;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0010

D;D;D;D;D;D;D;D;T

Sift4G

Uncertain

0.010

D;D;D;D;D;D;D;D;D

Polyphen

1.0

D;.;D;D;.;D;D;D;D

Vest4

0.52

MutPred

0.51

Gain of phosphorylation at P40 (P = 0.0419);Gain of phosphorylation at P40 (P = 0.0419);Gain of phosphorylation at P40 (P = 0.0419);Gain of phosphorylation at P40 (P = 0.0419);Gain of phosphorylation at P40 (P = 0.0419);Gain of phosphorylation at P40 (P = 0.0419);Gain of phosphorylation at P40 (P = 0.0419);Gain of phosphorylation at P40 (P = 0.0419);Gain of phosphorylation at P40 (P = 0.0419);

MVP

0.59

MPC

0.88

ClinPred

0.98

GERP RS

5.0

Varity_R

0.48

gMVP

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over