6-29660660-T-C

Variant names:

• chr6-29660660-T-C
• rs3135050
• NM_206809.4:c.436+994T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206809.4(MOG):​c.436+994T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 147,944 control chromosomes in the GnomAD database, including 57,222 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (57222 hom., cov: 25)
• Consequence: MOG NM_206809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOG	NM_206809.4	MANE Select	c.436+994T>C		intron	N/A	NP_996532.2
	MOG	NM_001363610.2		c.436+994T>C		intron	N/A	NP_001350539.1
	MOG	NM_002433.5		c.436+994T>C		intron	N/A	NP_002424.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOG	ENST00000376917.8	TSL:1 MANE Select	c.436+994T>C		intron	N/A	ENSP00000366115.3
	MOG	ENST00000376894.8	TSL:1	c.436+994T>C		intron	N/A	ENSP00000366091.4
	MOG	ENST00000376898.7	TSL:1	c.436+994T>C		intron	N/A	ENSP00000366095.3

Frequencies

GnomAD3 genomes AF: 0.876 AC: 129460 AN: 147834 Hom.: 57157 Cov.: 25

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.886

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.876 AC: 129581 AN: 147944 Hom.: 57222 Cov.: 25 AF XY: 0.872 AC XY: 62580 AN XY: 71744

African (AFR) AF: 0.956 AC: 37769 AN: 39522

American (AMR) AF: 0.913 AC: 13554 AN: 14838

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3030 AN: 3462

East Asian (EAS) AF: 0.977 AC: 4979 AN: 5096

South Asian (SAS) AF: 0.926 AC: 4296 AN: 4640

European-Finnish (FIN) AF: 0.684 AC: 6431 AN: 9408

Middle Eastern (MID) AF: 0.873 AC: 255 AN: 292

European-Non Finnish (NFE) AF: 0.837 AC: 56681 AN: 67732

Other (OTH) AF: 0.888 AC: 1816 AN: 2046

Alfa AF: 0.859 Hom.: 161752

Bravo AF: 0.896

Asia WGS AF: 0.949 AC: 3302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.75
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs3135050; hg19: chr6-29628437;