chr6-29659564-C-T

Variant names:

• chr6-29659564-C-T
• rs777633686
• NM_206809.4:c.334C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_206809.4(MOG):​c.334C>T​(p.Leu112Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L112L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: MOG NM_206809.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32
• Publications: 1 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOG	NM_206809.4	MANE Select	c.334C>T	p.Leu112Phe	missense	Exon 2 of 8	NP_996532.2	Q16653-1
	MOG	NM_001363610.2		c.334C>T	p.Leu112Phe	missense	Exon 2 of 7	NP_001350539.1	Q16653-13
	MOG	NM_002433.5		c.334C>T	p.Leu112Phe	missense	Exon 2 of 8	NP_002424.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOG	ENST00000376917.8	TSL:1 MANE Select	c.334C>T	p.Leu112Phe	missense	Exon 2 of 8	ENSP00000366115.3	Q16653-1
	MOG	ENST00000376894.8	TSL:1	c.334C>T	p.Leu112Phe	missense	Exon 2 of 7	ENSP00000366091.4	Q16653-13
	MOG	ENST00000376898.7	TSL:1	c.334C>T	p.Leu112Phe	missense	Exon 2 of 8	ENSP00000366095.3	Q16653-5

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000406 AC: 1 AN: 246608 AF XY: 0.00000744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000903

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460786 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726710

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.56	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Pathogenic	3.5	M
PhyloP100		2.3
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.86
MVP		0.82
MPC		0.91
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.55
gMVP		0.81
Mutation Taster		=47/53	disease causing

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

Other links and lift over

dbSNP: rs777633686; hg19: chr6-29627341;