6-29659445-C-A

Variant names:

• chr6-29659445-C-A
• rs138169338
• NM_206809.4:c.215C>A

Variant summary

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

The NM_206809.4(MOG):​c.215C>A​(p.Pro72His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,613,004 control chromosomes in the GnomAD database, including 478 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P72L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.013 (52 hom., cov: 31)
  • Exomes 𝑓: 0.012 (426 hom.)
• Consequence: MOG NM_206809.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06
• Publications: 8 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 (MetaRNN=0.0020365417).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0511 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.215C>A	p.Pro72His	missense	Exon 2 of 8	NP_996532.2	Q16653-1
	MOG	NM_001363610.2		c.215C>A	p.Pro72His	missense	Exon 2 of 7	NP_001350539.1	Q16653-13
	MOG	NM_002433.5		c.215C>A	p.Pro72His	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.215C>A	p.Pro72His	missense	Exon 2 of 8	ENSP00000366115.3	Q16653-1
	MOG	ENST00000376894.8	TSL:1	c.215C>A	p.Pro72His	missense	Exon 2 of 7	ENSP00000366091.4	Q16653-13
	MOG	ENST00000376898.7	TSL:1	c.215C>A	p.Pro72His	missense	Exon 2 of 8	ENSP00000366095.3	Q16653-5

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1928 AN: 152114 Hom.: 53 Cov.: 31

Gnomad AFR AF: 0.00244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0542

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0429

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00798

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.0247 AC: 6081 AN: 246576 AF XY: 0.0232

Gnomad AFR exome AF: 0.00152

Gnomad AMR exome AF: 0.0952

Gnomad ASJ exome AF: 0.0242

Gnomad EAS exome AF: 0.000602

Gnomad FIN exome AF: 0.0130

Gnomad NFE exome AF: 0.00713

Gnomad OTH exome AF: 0.0198

GnomAD4 exome AF: 0.0117 AC: 17027 AN: 1460772 Hom.: 426 Cov.: 31 AF XY: 0.0124 AC XY: 9034 AN XY: 726700

African (AFR) AF: 0.00149 AC: 50 AN: 33480

American (AMR) AF: 0.0888 AC: 3973 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 641 AN: 26136

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39700

South Asian (SAS) AF: 0.0441 AC: 3804 AN: 86258

European-Finnish (FIN) AF: 0.0141 AC: 735 AN: 52312

Middle Eastern (MID) AF: 0.00763 AC: 44 AN: 5768

European-Non Finnish (NFE) AF: 0.00637 AC: 7084 AN: 1112008

Other (OTH) AF: 0.0114 AC: 686 AN: 60386

GnomAD4 genome AF: 0.0127 AC: 1928 AN: 152232 Hom.: 52 Cov.: 31 AF XY: 0.0143 AC XY: 1067 AN XY: 74436

African (AFR) AF: 0.00243 AC: 101 AN: 41538

American (AMR) AF: 0.0542 AC: 828 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 72 AN: 3468

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5174

South Asian (SAS) AF: 0.0427 AC: 206 AN: 4826

European-Finnish (FIN) AF: 0.0139 AC: 147 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00798 AC: 543 AN: 68010

Other (OTH) AF: 0.0128 AC: 27 AN: 2116

Alfa AF: 0.00850 Hom.: 28

Bravo AF: 0.0143

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00830 AC: 32

ESP6500AA AF: 0.00331 AC: 10

ESP6500EA AF: 0.00849 AC: 46

ExAC AF: 0.0217 AC: 2561

EpiCase AF: 0.00589

EpiControl AF: 0.00735

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	N
PhyloP100		3.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.19
Sift	Benign	0.19	T
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.21
MPC		0.92
ClinPred		0.027	T
GERP RS		4.8
Varity_R		0.22
gMVP		0.52
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs138169338; hg19: chr6-29627222; COSMIC: COSV65321538;