chr6-29659566-C-T

Variant names:

• chr6-29659566-C-T
• rs150910417
• NM_206809.4:c.336C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_206809.4(MOG):​c.336C>T​(p.Leu112Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000906 in 1,613,096 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00093 (1 hom.)
• Consequence: MOG NM_206809.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.417
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 6-29659566-C-T is Benign according to our data. Variant chr6-29659566-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3257658.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.417 with no splicing effect.

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.336C>T	p.Leu112Leu	synonymous	Exon 2 of 8	NP_996532.2	Q16653-1
	MOG	NM_001363610.2		c.336C>T	p.Leu112Leu	synonymous	Exon 2 of 7	NP_001350539.1	Q16653-13
	MOG	NM_002433.5		c.336C>T	p.Leu112Leu	synonymous	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.336C>T	p.Leu112Leu	synonymous	Exon 2 of 8	ENSP00000366115.3	Q16653-1
	MOG	ENST00000376894.8	TSL:1	c.336C>T	p.Leu112Leu	synonymous	Exon 2 of 7	ENSP00000366091.4	Q16653-13
	MOG	ENST00000376898.7	TSL:1	c.336C>T	p.Leu112Leu	synonymous	Exon 2 of 8	ENSP00000366095.3	Q16653-5

Frequencies

GnomAD3 genomes AF: 0.000683 AC: 104 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00128

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000710 AC: 175 AN: 246606 AF XY: 0.000744

Gnomad AFR exome AF: 0.000331

Gnomad AMR exome AF: 0.000812

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00117

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000929 AC: 1357 AN: 1460784 Hom.: 1 Cov.: 31 AF XY: 0.000915 AC XY: 665 AN XY: 726708

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.000850 AC: 38 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: 0.0000580 AC: 5 AN: 86256

European-Finnish (FIN) AF: 0.000344 AC: 18 AN: 52324

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

European-Non Finnish (NFE) AF: 0.00111 AC: 1239 AN: 1112010

Other (OTH) AF: 0.000828 AC: 50 AN: 60386

GnomAD4 genome AF: 0.000683 AC: 104 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000631 AC XY: 47 AN XY: 74474

African (AFR) AF: 0.000217 AC: 9 AN: 41558

American (AMR) AF: 0.000392 AC: 6 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00128 AC: 87 AN: 68026

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000930 Hom.: 0

Bravo AF: 0.000722

EpiCase AF: 0.000927

EpiControl AF: 0.00142

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
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.7
DANN	Benign	0.71
PhyloP100		0.42
Mutation Taster		=99/1	polymorphism

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: rs150910417; hg19: chr6-29627343;