rs370604035

Variant names:

• chr6-29670786-A-G
• rs370604035
• ENST00000376894.8:c.795A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001363610.2(MOG):​c.795A>G​(p.Thr265Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,601,004 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0022 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (5 hom.)
• Consequence: MOG NM_001363610.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.547

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-29670786-A-G is Benign according to our data. Variant chr6-29670786-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3033947.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.547 with no splicing effect.
• BS2: High AC in GnomAd4 at 337 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOG	NM_206809.4	c.730+65A>G		intron_variant	Intron 7 of 7	ENST00000376917.8	NP_996532.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOG	ENST00000376917.8	c.730+65A>G		intron_variant	Intron 7 of 7	1	NM_206809.4	ENSP00000366115.3

Frequencies

GnomAD3 genomes AF: 0.00217 AC: 330 AN: 152222 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00641

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00184

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00158 AC: 352 AN: 222384 Hom.: 2 AF XY: 0.00159 AC XY: 192 AN XY: 121016

Gnomad AFR exome AF: 0.00120

Gnomad AMR exome AF: 0.00213

Gnomad ASJ exome AF: 0.000107

Gnomad EAS exome AF: 0.00273

Gnomad SAS exome AF: 0.000355

Gnomad FIN exome AF: 0.0000485

Gnomad NFE exome AF: 0.00201

Gnomad OTH exome AF: 0.00283

GnomAD4 exome AF: 0.00125 AC: 1817 AN: 1448664 Hom.: 5 Cov.: 33 AF XY: 0.00126 AC XY: 910 AN XY: 719446

Gnomad4 AFR exome AF: 0.00206

Gnomad4 AMR exome AF: 0.00226

Gnomad4 ASJ exome AF: 0.000194

Gnomad4 EAS exome AF: 0.00134

Gnomad4 SAS exome AF: 0.000260

Gnomad4 FIN exome AF: 0.0000966

Gnomad4 NFE exome AF: 0.00126

Gnomad4 OTH exome AF: 0.00172

GnomAD4 genome AF: 0.00221 AC: 337 AN: 152340 Hom.: 8 Cov.: 32 AF XY: 0.00243 AC XY: 181 AN XY: 74502

Gnomad4 AFR AF: 0.00221

Gnomad4 AMR AF: 0.00640

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00184

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00175 Hom.: 1

Bravo AF: 0.00232

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MOG-related disorder Benign:1

May 15, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.75

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: rs370604035; hg19: chr6-29638563;