Variant rs3130253 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_206809.4(MOG):c.520A>G(p.Ile174Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 1,611,296 control chromosomes in the GnomAD database, including 689,855 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.95 ( 68469 hom., cov: 29)

Exomes 𝑓: 0.92 ( 621386 hom. )

Consequence

MOG
NM_206809.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.307

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.703643E-7).

BP6

Variant 6-29666235-A-G is Benign according to our data. Variant chr6-29666235-A-G is described in ClinVar as [Benign]. Clinvar id is 3060512.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-29666235-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOG	NM_206809.4 link	c.520A>G	p.Ile174Val	missense_variant	Exon 3 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.520A>G	p.Ile174Val	missense_variant	Exon 3 of 8	1	NM_206809.4	ENSP00000366115.3		Q16653-1

Frequencies

GnomAD3 genomes

AF:

0.948

AC:

144112

AN:

152034

Hom.:

68408

Cov.:

show subpopulations

Gnomad AFR

AF:

0.986

Gnomad AMI

AF:

0.956

Gnomad AMR

AF:

0.957

Gnomad ASJ

AF:

0.982

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.989

Gnomad FIN

AF:

0.942

Gnomad MID

AF:

0.972

Gnomad NFE

AF:

0.915

Gnomad OTH

AF:

0.950

GnomAD3 exomes

AF:

0.949

AC:

233912

AN:

246482

Hom.:

111147

AF XY:

0.950

AC XY:

127537

AN XY:

134312

show subpopulations

Gnomad AFR exome

AF:

0.987

Gnomad AMR exome

AF:

0.972

Gnomad ASJ exome

AF:

0.979

Gnomad EAS exome

AF:

0.998

Gnomad SAS exome

AF:

0.985

Gnomad FIN exome

AF:

0.936

Gnomad NFE exome

AF:

0.919

Gnomad OTH exome

AF:

0.941

GnomAD4 exome

AF:

0.922

AC:

1345753

AN:

1459144

Hom.:

621386

Cov.:

AF XY:

0.924

AC XY:

671118

AN XY:

725974

show subpopulations

Gnomad4 AFR exome

AF:

0.987

Gnomad4 AMR exome

AF:

0.970

Gnomad4 ASJ exome

AF:

0.980

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.985

Gnomad4 FIN exome

AF:

0.935

Gnomad4 NFE exome

AF:

0.908

Gnomad4 OTH exome

AF:

0.933

GnomAD4 genome

AF:

0.948

AC:

144232

AN:

152152

Hom.:

68469

Cov.:

AF XY:

0.950

AC XY:

70633

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.986

Gnomad4 AMR

AF:

0.957

Gnomad4 ASJ

AF:

0.982

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.989

Gnomad4 FIN

AF:

0.942

Gnomad4 NFE

AF:

0.915

Gnomad4 OTH

AF:

0.951

Alfa

AF:

0.927

Hom.:

131688

Bravo

AF:

0.951

TwinsUK

AF:

0.914

AC:

3388

ALSPAC

AF:

0.907

AC:

3497

ESP6500AA

AF:

0.981

AC:

2965

ESP6500EA

AF:

0.911

AC:

4937

ExAC

AF:

0.949

AC:

111903

Asia WGS

AF:

0.991

AC:

3446

AN:

3478

EpiCase

AF:

0.925

EpiControl

AF:

0.926

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MOG-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.031

DANN

Benign

0.26

DEOGEN2

Benign

0.024

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

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.18

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

MetaRNN

Benign

6.7e-7

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

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.90

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

PrimateAI

Benign

0.33

PROVEAN

Benign

0.040

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

REVEL

Benign

0.052

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.0

B;B;.;B;B;.;.;B;B;B;B

Vest4

0.034

MPC

0.20

ClinPred

0.0013

GERP RS

1.7

Varity_R

0.022

gMVP

0.19

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over