6-29670862-ACTC-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

The ENST00000376894.8(MOG):c.877_879del(p.Pro293del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000558 in 1,581,104 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00057 (6 hom.)
• Consequence: MOG ENST00000376894.8 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.167

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 Likely_benign. Variant got -5 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in ENST00000376894.8. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 6-29670862-ACTC-A is Benign according to our data. Variant chr6-29670862-ACTC-A is described in ClinVar as [Benign]. Clinvar id is 3048015.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOG	NM_206809.4	c.730+147_730+149del		intron_variant		ENST00000376917.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOG	ENST00000376917.8	c.730+147_730+149del		intron_variant		1	NM_206809.4	P1

Frequencies

GnomAD3 genomes AF: 0.000409 AC: 62 AN: 151716 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00563

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000383

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00103 AC: 198 AN: 193072 Hom.: 3 AF XY: 0.00127 AC XY: 133 AN XY: 104864

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000471

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00517

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000569

Gnomad OTH exome AF: 0.000785

GnomAD4 exome AF: 0.000574 AC: 821 AN: 1429270 Hom.: 6 AF XY: 0.000730 AC XY: 517 AN XY: 708226

Gnomad4 AFR exome AF: 0.0000303

Gnomad4 AMR exome AF: 0.000440

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000259

Gnomad4 SAS exome AF: 0.00542

Gnomad4 FIN exome AF: 0.0000198

Gnomad4 NFE exome AF: 0.000273

Gnomad4 OTH exome AF: 0.000692

GnomAD4 genome AF: 0.000408 AC: 62 AN: 151834 Hom.: 0 Cov.: 32 AF XY: 0.000539 AC XY: 40 AN XY: 74210

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000394

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00563

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000383

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000291 Hom.: 0

Bravo AF: 0.000325

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MOG-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 21, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs537236203; hg19: chr6-29638639;