6-29670324-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_206809.4(MOG):c.636T>C(p.Phe212=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 1,614,190 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 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (11 hom.)
• Consequence: MOG NM_206809.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.314

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 6-29670324-T-C is Benign according to our data. Variant chr6-29670324-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2656323.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-29670324-T-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.314 with no splicing effect.
• BS2: High AC in GnomAd at 425 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOG	NM_206809.4	c.636T>C	p.Phe212=	synonymous_variant	6/8	ENST00000376917.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOG	ENST00000376917.8	c.636T>C	p.Phe212=	synonymous_variant	6/8	1	NM_206809.4	P1

Frequencies

GnomAD3 genomes AF: 0.00279 AC: 425 AN: 152178 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00360

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00277 AC: 697 AN: 251496 Hom.: 5 AF XY: 0.00268 AC XY: 364 AN XY: 135922

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000425

Gnomad FIN exome AF: 0.0161

Gnomad NFE exome AF: 0.00273

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00253 AC: 3701 AN: 1461894 Hom.: 11 Cov.: 31 AF XY: 0.00258 AC XY: 1878 AN XY: 727248

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000429

Gnomad4 FIN exome AF: 0.0145

Gnomad4 NFE exome AF: 0.00247

Gnomad4 OTH exome AF: 0.00185

GnomAD4 genome AF: 0.00279 AC: 425 AN: 152296 Hom.: 1 Cov.: 32 AF XY: 0.00294 AC XY: 219 AN XY: 74458

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.00360

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00281 Hom.: 1

Bravo AF: 0.00179

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

MOG: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	7.4
Dann	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs112913018; hg19: chr6-29638101;