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GeneBe

6-29659536-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_206809.4(MOG):c.306A>G(p.Lys102=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,613,114 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0087 ( 8 hom., cov: 31)
Exomes 𝑓: 0.013 ( 162 hom. )

Consequence

MOG
NM_206809.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0190
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-29659536-A-G is Benign according to our data. Variant chr6-29659536-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3056332.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=-0.019 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0129 (18796/1460778) while in subpopulation MID AF= 0.021 (121/5768). AF 95% confidence interval is 0.0179. There are 162 homozygotes in gnomad4_exome. There are 9352 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
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 1329 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MOGNM_206809.4 linkuse as main transcriptc.306A>G p.Lys102= synonymous_variant 2/8 ENST00000376917.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MOGENST00000376917.8 linkuse as main transcriptc.306A>G p.Lys102= synonymous_variant 2/81 NM_206809.4 P1Q16653-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00873
AC:
1329
AN:
152218
Hom.:
8
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00207
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00923
Gnomad ASJ
AF:
0.00548
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00476
Gnomad FIN
AF:
0.00348
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.0147
Gnomad OTH
AF:
0.00860
GnomAD3 exomes
AF:
0.00955
AC:
2356
AN:
246652
Hom.:
25
AF XY:
0.0102
AC XY:
1369
AN XY:
134424
show subpopulations
Gnomad AFR exome
AF:
0.00185
Gnomad AMR exome
AF:
0.00539
Gnomad ASJ exome
AF:
0.00431
Gnomad EAS exome
AF:
0.0000547
Gnomad SAS exome
AF:
0.00570
Gnomad FIN exome
AF:
0.00453
Gnomad NFE exome
AF:
0.0158
Gnomad OTH exome
AF:
0.0122
GnomAD4 exome
AF:
0.0129
AC:
18796
AN:
1460778
Hom.:
162
Cov.:
31
AF XY:
0.0129
AC XY:
9352
AN XY:
726706
show subpopulations
Gnomad4 AFR exome
AF:
0.00212
Gnomad4 AMR exome
AF:
0.00597
Gnomad4 ASJ exome
AF:
0.00459
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.00584
Gnomad4 FIN exome
AF:
0.00552
Gnomad4 NFE exome
AF:
0.0150
Gnomad4 OTH exome
AF:
0.0119
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00871
AC:
1327
AN:
152336
Hom.:
8
Cov.:
31
AF XY:
0.00820
AC XY:
611
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.00207
Gnomad4 AMR
AF:
0.00921
Gnomad4 ASJ
AF:
0.00548
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00477
Gnomad4 FIN
AF:
0.00348
Gnomad4 NFE
AF:
0.0146
Gnomad4 OTH
AF:
0.00851
Alfa
AF:
0.0125
Hom.:
6
Bravo
AF:
0.00921
Asia WGS
AF:
0.00289
AC:
10
AN:
3478
EpiCase
AF:
0.0199
EpiControl
AF:
0.0195

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 SciencesFeb 14, 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
-0.60
Cadd
Benign
3.2
Dann
Benign
0.35

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: rs34758289; hg19: chr6-29627313; API