rs3130253

Variant names:

• chr6-29666235-A-C
• rs3130253
• NM_206809.4:c.520A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-29666235-A-C
• chr6-29666235-A-G
• chr6-29666235-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001363610.2(MOG):​c.520A>C​(p.Ile174Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I174V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MOG NM_001363610.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0585697).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOG	NM_206809.4	MANE Select	c.520A>C	p.Ile174Leu	missense	Exon 3 of 8	NP_996532.2
	MOG	NM_001363610.2		c.520A>C	p.Ile174Leu	missense	Exon 3 of 7	NP_001350539.1
	MOG	NM_002433.5		c.520A>C	p.Ile174Leu	missense	Exon 3 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.520A>C	p.Ile174Leu	missense	Exon 3 of 8	ENSP00000366115.3
	MOG	ENST00000376894.8	TSL:1	c.520A>C	p.Ile174Leu	missense	Exon 3 of 7	ENSP00000366091.4
	MOG	ENST00000376898.7	TSL:1	c.520A>C	p.Ile174Leu	missense	Exon 3 of 8	ENSP00000366095.3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460002 Hom.: 0 Cov.: 42 AF XY: 0.00000138 AC XY: 1 AN XY: 726370

African (AFR) AF: 0.00 AC: 0 AN: 33470

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111302

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.36
DANN	Benign	0.91
DEOGEN2	Benign	0.051	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-0.31
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.059
Sift	Benign	0.14	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.67		Gain of sheet (P = 0.039)
MVP		0.16
MPC		0.24
ClinPred		0.057	T
GERP RS		1.7
Varity_R		0.052
gMVP		0.34
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs3130253; hg19: chr6-29634012;