6-29670386-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_206809.4(MOG):c.698G>A(p.Arg233Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000162 in 1,614,094 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (6 hom.)
• Consequence: MOG NM_206809.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.80

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03815064).
• BS2: High AC in GnomAd at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOG	NM_206809.4	c.698G>A	p.Arg233Gln	missense_variant	6/8	ENST00000376917.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOG	ENST00000376917.8	c.698G>A	p.Arg233Gln	missense_variant	6/8	1	NM_206809.4	P1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000147 AC: 37 AN: 251472 Hom.: 0 AF XY: 0.000103 AC XY: 14 AN XY: 135912

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00120

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000814

GnomAD4 exome AF: 0.000161 AC: 235 AN: 1461820 Hom.: 6 Cov.: 31 AF XY: 0.000133 AC XY: 97 AN XY: 727216

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00103

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.00253

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152274 Hom.: 1 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74450

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000203 Hom.: 0

Bravo AF: 0.000200

ExAC AF: 0.000140 AC: 17

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 11, 2023

The c.698G>A (p.R233Q) alteration is located in exon 6 (coding exon 6) of the MOG gene. This alteration results from a G to A substitution at nucleotide position 698, causing the arginine (R) at amino acid position 233 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.35
Cadd	Uncertain	25
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.030	T;.;.;T;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.038	T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.0	L;.;L;.;L
MutationTaster	Benign	0.52	D;D;D;D;D;D;D;D;D;D;N;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.090	N;D;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0070	D;D;D;T;D
Sift4G	Benign	0.37	T;T;T;T;T
Polyphen		0.95	P;D;.;.;D
Vest4		0.32
MVP		0.63
MPC		0.86
ClinPred		0.11	T
GERP RS		5.7
Varity_R		0.20
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs375219482; hg19: chr6-29638163; COSMIC: COSV65306484; COSMIC: COSV65306484;