6-29657224-A-G

Variant names:

• chr6-29657224-A-G
• rs3130250
• NM_206809.4:c.15A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001363610.2(MOG):​c.15A>G​(p.Ser5Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 1,609,366 control chromosomes in the GnomAD database, including 591,631 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 (58645 hom., cov: 29)
  • Exomes 𝑓: 0.85 (532986 hom.)
• Consequence: MOG NM_001363610.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422
• Publications: 40 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=-0.422 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363610.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOG	NM_206809.4	MANE Select	c.15A>G	p.Ser5Ser	synonymous	Exon 1 of 8	NP_996532.2
	MOG	NM_001363610.2		c.15A>G	p.Ser5Ser	synonymous	Exon 1 of 7	NP_001350539.1
	MOG	NM_002433.5		c.15A>G	p.Ser5Ser	synonymous	Exon 1 of 8	NP_002424.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOG	ENST00000376917.8	TSL:1 MANE Select	c.15A>G	p.Ser5Ser	synonymous	Exon 1 of 8	ENSP00000366115.3
	MOG	ENST00000376894.8	TSL:1	c.15A>G	p.Ser5Ser	synonymous	Exon 1 of 7	ENSP00000366091.4
	MOG	ENST00000376898.7	TSL:1	c.15A>G	p.Ser5Ser	synonymous	Exon 1 of 8	ENSP00000366095.3

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133039 AN: 151914 Hom.: 58597 Cov.: 29

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.886

GnomAD2 exomes AF: 0.879 AC: 215352 AN: 245056 AF XY: 0.878

Gnomad AFR exome AF: 0.937

Gnomad AMR exome AF: 0.941

Gnomad ASJ exome AF: 0.888

Gnomad EAS exome AF: 0.988

Gnomad FIN exome AF: 0.730

Gnomad NFE exome AF: 0.843

Gnomad OTH exome AF: 0.866

GnomAD4 exome AF: 0.854 AC: 1244192 AN: 1457334 Hom.: 532986 Cov.: 42 AF XY: 0.857 AC XY: 621206 AN XY: 725046

African (AFR) AF: 0.934 AC: 31228 AN: 33428

American (AMR) AF: 0.938 AC: 41808 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 23111 AN: 26056

East Asian (EAS) AF: 0.992 AC: 39390 AN: 39694

South Asian (SAS) AF: 0.947 AC: 81403 AN: 85962

European-Finnish (FIN) AF: 0.739 AC: 38577 AN: 52224

Middle Eastern (MID) AF: 0.882 AC: 5078 AN: 5758

European-Non Finnish (NFE) AF: 0.839 AC: 931295 AN: 1109364

Other (OTH) AF: 0.868 AC: 52302 AN: 60266

GnomAD4 genome AF: 0.876 AC: 133146 AN: 152032 Hom.: 58645 Cov.: 29 AF XY: 0.873 AC XY: 64860 AN XY: 74300

African (AFR) AF: 0.934 AC: 38717 AN: 41468

American (AMR) AF: 0.915 AC: 13982 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3048 AN: 3470

East Asian (EAS) AF: 0.982 AC: 5065 AN: 5158

South Asian (SAS) AF: 0.957 AC: 4618 AN: 4824

European-Finnish (FIN) AF: 0.716 AC: 7559 AN: 10562

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.842 AC: 57245 AN: 67952

Other (OTH) AF: 0.887 AC: 1874 AN: 2112

Alfa AF: 0.861 Hom.: 218694

Bravo AF: 0.893

Asia WGS AF: 0.962 AC: 3347 AN: 3478

EpiCase AF: 0.851

EpiControl AF: 0.856

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.98
DANN	Benign	0.48
PhyloP100		-0.42
PromoterAI		0.042	Neutral
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: rs3130250; hg19: chr6-29625001; COSMIC: COSV65320756; COSMIC: COSV65320756;