6-29657229-C-T

Variant names:

• chr6-29657229-C-T
• rs774294291
• NM_206809.4:c.20C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_206809.4(MOG):​c.20C>T​(p.Pro7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P7H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: MOG NM_206809.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07347864).

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.20C>T	p.Pro7Leu	missense	Exon 1 of 8	NP_996532.2	Q16653-1
	MOG	NM_001363610.2		c.20C>T	p.Pro7Leu	missense	Exon 1 of 7	NP_001350539.1	Q16653-13
	MOG	NM_002433.5		c.20C>T	p.Pro7Leu	missense	Exon 1 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.20C>T	p.Pro7Leu	missense	Exon 1 of 8	ENSP00000366115.3	Q16653-1
	MOG	ENST00000376894.8	TSL:1	c.20C>T	p.Pro7Leu	missense	Exon 1 of 7	ENSP00000366091.4	Q16653-13
	MOG	ENST00000376898.7	TSL:1	c.20C>T	p.Pro7Leu	missense	Exon 1 of 8	ENSP00000366095.3	Q16653-5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459232 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 725838

African (AFR) AF: 0.000149 AC: 5 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 85962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111100

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.6
DANN	Benign	0.54
DEOGEN2	Benign	0.059	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.46
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.017
Sift	Uncertain	0.012	D
Sift4G	Benign	0.098	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.32		Loss of relative solvent accessibility (P = 0.008)
MVP		0.36
MPC		0.24
ClinPred		0.038	T
GERP RS		0.46
PromoterAI		0.0063	Neutral
Varity_R		0.038
gMVP		0.38
Mutation Taster		=100/0	polymorphism

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: rs774294291; hg19: chr6-29625006;