Variant 6-29666226-G-C 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.511G>C(p.Val171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,610,262 control chromosomes in the GnomAD database, including 40,265 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3156 hom., cov: 31)

Exomes 𝑓: 0.22 ( 37109 hom. )

Consequence

MOG
NM_206809.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.303

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=0.008852869).

BP6

Variant 6-29666226-G-C is Benign according to our data. Variant chr6-29666226-G-C is described in ClinVar as [Benign]. Clinvar id is 3059372.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOG	NM_206809.4 linkuse as main transcript	c.511G>C	p.Val171Leu	missense_variant	3/8	ENST00000376917.8	NP_996532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOG	ENST00000376917.8 linkuse as main transcript	c.511G>C	p.Val171Leu	missense_variant	3/8	1	NM_206809.4	ENSP00000366115	P1	Q16653-1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29517

AN:

151918

Hom.:

3155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.267

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.273

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.160

GnomAD3 exomes

AF:

0.222

AC:

54792

AN:

246528

Hom.:

6857

AF XY:

0.216

AC XY:

29005

AN XY:

134334

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.253

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.290

Gnomad SAS exome

AF:

0.0998

Gnomad FIN exome

AF:

0.301

Gnomad NFE exome

AF:

0.242

Gnomad OTH exome

AF:

0.203

GnomAD4 exome

AF:

0.220

AC:

320474

AN:

1458228

Hom.:

37109

Cov.:

AF XY:

0.217

AC XY:

157182

AN XY:

725530

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.238

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.265

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.229

Gnomad4 OTH exome

AF:

0.202

GnomAD4 genome

AF:

0.194

AC:

29520

AN:

152034

Hom.:

3156

Cov.:

AF XY:

0.195

AC XY:

14464

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.183

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.272

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.292

Gnomad4 NFE

AF:

0.232

Gnomad4 OTH

AF:

0.159

Alfa

AF:

0.222

Hom.:

2973

Bravo

AF:

0.186

TwinsUK

AF:

0.232

AC:

861

ALSPAC

AF:

0.242

AC:

934

ESP6500AA

AF:

0.122

AC:

368

ESP6500EA

AF:

0.228

AC:

1233

ExAC

AF:

0.220

AC:

26034

Asia WGS

AF:

0.165

AC:

572

AN:

3478

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 28, 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

0.12

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.8

DANN

Benign

0.96

DEOGEN2

Benign

0.041

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

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.70

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

MetaRNN

Benign

0.0089

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;.;L;L;.;.;L;L;L;L;L

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P;P;P;P;P;P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.53

N;N;N;N;D;N;N;N;N;N;N

REVEL

Benign

0.039

Sift

Benign

0.38

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

Sift4G

Benign

0.27

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

Polyphen

0.0040

B;B;.;B;B;.;.;B;B;P;B

Vest4

0.14

MPC

0.24

ClinPred

0.0040

GERP RS

0.63

Varity_R

0.054

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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