6-29666235-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.95 (68469 hom., cov: 29)
  • Exomes 𝑓: 0.92 (621386 hom.)
• Consequence: MOG NM_206809.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.307

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]

ACMG classification

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
MOG	NM_206809.4	c.520A>G	p.Ile174Val	missense_variant	3/8	ENST00000376917.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOG	ENST00000376917.8	c.520A>G	p.Ile174Val	missense_variant	3/8	1	NM_206809.4	P1

Frequencies

GnomAD3 genomes AF: 0.948 AC: 144112 AN: 152034 Hom.: 68408 Cov.: 29

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

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.: 42 AF XY: 0.924 AC XY: 671118 AN XY: 725974

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.: 29 AF XY: 0.950 AC XY: 70633 AN XY: 74376

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: criteria provided, single submitter

Submissions by phenotype

MOG-related disorder Benign:1

Benign, criteria provided, single submitter

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	T
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	N
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	T
MutationAssessor	Benign	-0.90	N;.;N;N;.;.;N;N;N;N;N
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P;P;P;P;P
PrimateAI	Benign	0.33	T
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	T
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

Other links and lift over

dbSNP: rs3130253; hg19: chr6-29634012; COSMIC: COSV65321022; COSMIC: COSV65321022;