Genetic Variant NM_206809.4:c.215C>A (chr6-29659445-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_206809.4(MOG):c.215C>A(p.Pro72His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,613,004 control chromosomes in the GnomAD database, including 478 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.013 ( 52 hom., cov: 31)

Exomes 𝑓: 0.012 ( 426 hom. )

Consequence

MOG
NM_206809.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.06

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020365417).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOG	NM_206809.4 link	c.215C>A	p.Pro72His	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.215C>A	p.Pro72His	missense_variant	Exon 2 of 8	1	NM_206809.4	ENSP00000366115.3		Q16653-1

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1928

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0542

Gnomad ASJ

AF:

0.0208

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0429

Gnomad FIN

AF:

0.0139

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00798

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0247

AC:

6081

AN:

246576

Hom.:

260

AF XY:

0.0232

AC XY:

3114

AN XY:

134394

show subpopulations

Gnomad AFR exome

AF:

0.00152

Gnomad AMR exome

AF:

0.0952

Gnomad ASJ exome

AF:

0.0242

Gnomad EAS exome

AF:

0.000602

Gnomad SAS exome

AF:

0.0439

Gnomad FIN exome

AF:

0.0130

Gnomad NFE exome

AF:

0.00713

Gnomad OTH exome

AF:

0.0198

GnomAD4 exome

AF:

0.0117

AC:

17027

AN:

1460772

Hom.:

426

Cov.:

AF XY:

0.0124

AC XY:

9034

AN XY:

726700

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.0888

Gnomad4 ASJ exome

AF:

0.0245

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0441

Gnomad4 FIN exome

AF:

0.0141

Gnomad4 NFE exome

AF:

0.00637

Gnomad4 OTH exome

AF:

0.0114

GnomAD4 genome

AF:

0.0127

AC:

1928

AN:

152232

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1067

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00243

Gnomad4 AMR

AF:

0.0542

Gnomad4 ASJ

AF:

0.0208

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.0427

Gnomad4 FIN

AF:

0.0139

Gnomad4 NFE

AF:

0.00798

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00757

Hom.:

Bravo

AF:

0.0143

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00331

AC:

ESP6500EA

AF:

0.00849

AC:

ExAC

AF:

0.0217

AC:

2561

EpiCase

AF:

0.00589

EpiControl

AF:

0.00735

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

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

Eigen

Benign

0.11

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.52

T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.14

N;N;N;.;N;N;N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.18

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.19

T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.16

T;T;T;T;T;T;T;T;T

Polyphen

1.0

D;.;D;D;.;B;D;D;D

Vest4

0.21

MPC

0.92

ClinPred

0.027

GERP RS

4.8

Varity_R

0.22

gMVP

0.52

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

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