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GeneBe

6-29670786-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000376894.8(MOG):c.795A>G(p.Thr265=) 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 (★).

Frequency

Genomes: 𝑓 0.0022 ( 8 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 5 hom. )

Consequence

MOG
ENST00000376894.8 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.547
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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 criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.547 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 330 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MOGNM_206809.4 linkuse as main transcriptc.730+65A>G intron_variant ENST00000376917.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MOGENST00000376917.8 linkuse as main transcriptc.730+65A>G intron_variant 1 NM_206809.4 P1Q16653-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00217
AC:
330
AN:
152222
Hom.:
7
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00221
AC:
337
AN:
152340
Hom.:
8
Cov.:
32
AF XY:
0.00243
AC XY:
181
AN XY:
74502
show subpopulations
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

MOG-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMay 15, 2020This 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs370604035; hg19: chr6-29638563; API