6-29659445-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_206809.4(MOG):​c.215C>T​(p.Pro72Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000487 in 1,613,006 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00049 (11 hom.)
• Consequence: MOG NM_206809.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007583916).
• BP6: Variant 6-29659445-C-T is Benign according to our data. Variant chr6-29659445-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3250856.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 11 Unknown gene

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>T	p.Pro72Leu	missense	Exon 2 of 8	NP_996532.2	Q16653-1
	MOG	NM_001363610.2		c.215C>T	p.Pro72Leu	missense	Exon 2 of 7	NP_001350539.1	Q16653-13
	MOG	NM_002433.5		c.215C>T	p.Pro72Leu	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>T	p.Pro72Leu	missense	Exon 2 of 8	ENSP00000366115.3	Q16653-1
	MOG	ENST00000376894.8	TSL:1	c.215C>T	p.Pro72Leu	missense	Exon 2 of 7	ENSP00000366091.4	Q16653-13
	MOG	ENST00000376898.7	TSL:1	c.215C>T	p.Pro72Leu	missense	Exon 2 of 8	ENSP00000366095.3	Q16653-5

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 152116 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000969 AC: 239 AN: 246576 AF XY: 0.00121

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000904

Gnomad OTH exome AF: 0.000659

GnomAD4 exome AF: 0.000491 AC: 717 AN: 1460772 Hom.: 11 Cov.: 31 AF XY: 0.000678 AC XY: 493 AN XY: 726700

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00781 AC: 674 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112008

Other (OTH) AF: 0.000613 AC: 37 AN: 60386

GnomAD4 genome AF: 0.000447 AC: 68 AN: 152234 Hom.: 1 Cov.: 31 AF XY: 0.000658 AC XY: 49 AN XY: 74438

African (AFR) AF: 0.0000963 AC: 4 AN: 41538

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.0133 AC: 64 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000104 Hom.: 28

Bravo AF: 0.000102

ExAC AF: 0.00115 AC: 135

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0076	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.29	N
PhyloP100		3.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.19
Sift	Benign	0.090	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.36
MutPred		0.44		Gain of MoRF binding (P = 0.0405)
MVP		0.64
MPC		0.86
ClinPred		0.098	T
GERP RS		4.8
Varity_R		0.15
gMVP		0.55
Mutation Taster		=95/5	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: rs138169338; hg19: chr6-29627222;