6-29666235-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

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

Publications

47 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3060512.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

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

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
MOG	NM_206809.4	MANE Select	c.520A>G	p.Ile174Val	missense	Exon 3 of 8	NP_996532.2
MOG	NM_001363610.2		c.520A>G	p.Ile174Val	missense	Exon 3 of 7	NP_001350539.1
MOG	NM_002433.5		c.520A>G	p.Ile174Val	missense	Exon 3 of 8	NP_002424.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MOG	ENST00000376917.8	TSL:1 MANE Select	c.520A>G	p.Ile174Val	missense	Exon 3 of 8	ENSP00000366115.3
MOG	ENST00000376894.8	TSL:1	c.520A>G	p.Ile174Val	missense	Exon 3 of 7	ENSP00000366091.4
MOG	ENST00000376898.7	TSL:1	c.520A>G	p.Ile174Val	missense	Exon 3 of 8	ENSP00000366095.3

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

GnomAD2 exomes

AF:

0.949

AC:

233912

AN:

246482

AF XY:

0.950

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 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

African (AFR)

AF:

0.987

AC:

33049

AN:

33470

American (AMR)

AF:

0.970

AC:

43366

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.980

AC:

25604

AN:

26130

East Asian (EAS)

AF:

0.999

AC:

39651

AN:

39698

South Asian (SAS)

AF:

0.985

AC:

84993

AN:

86248

European-Finnish (FIN)

AF:

0.935

AC:

48908

AN:

52300

Middle Eastern (MID)

AF:

0.970

AC:

5591

AN:

5764

European-Non Finnish (NFE)

AF:

0.908

AC:

1008302

AN:

1110470

Other (OTH)

AF:

0.933

AC:

56289

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

4632

9265

13897

18530

23162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21438

42876

64314

85752

107190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.948

AC:

144232

AN:

152152

Hom.:

68469

Cov.:

AF XY:

0.950

AC XY:

70633

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.986

AC:

40931

AN:

41518

American (AMR)

AF:

0.957

AC:

14594

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.982

AC:

3407

AN:

3470

East Asian (EAS)

AF:

0.998

AC:

5167

AN:

5176

South Asian (SAS)

AF:

0.989

AC:

4764

AN:

4816

European-Finnish (FIN)

AF:

0.942

AC:

9970

AN:

10588

Middle Eastern (MID)

AF:

0.969

AC:

285

AN:

294

European-Non Finnish (NFE)

AF:

0.915

AC:

62236

AN:

68012

Other (OTH)

AF:

0.951

AC:

2006

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

383

766

1150

1533

1916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.929

Hom.:

296276

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

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.031

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.024

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.18

MetaRNN

Benign

6.7e-7

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.90

PhyloP100

-0.31

PrimateAI

Benign

0.33

PROVEAN

Benign

0.040

REVEL

Benign

0.052

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.034

MPC

0.20

ClinPred

0.0013

GERP RS

1.7

Varity_R

0.022

gMVP

0.19

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over