ENST00000376889.3:n.*1425T>C – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000376889.3(MOG):n.*1425T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 161,116 control chromosomes in the GnomAD database, including 62,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.88 ( 58874 hom., cov: 27)

Exomes 𝑓: 0.85 ( 3505 hom. )

Consequence

MOG
ENST00000376889.3 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.52

Publications

4 publications found

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]

MOG links:

ZFP57 (HGNC:18791): (ZFP57 zinc finger protein) The protein encoded by this gene is a zinc finger protein containing a KRAB domain. Studies in mouse suggest that this protein may function as a transcriptional repressor. Mutations in this gene have been associated with transient neonatal diabetes mellitus type 1 (TNDM1).[provided by RefSeq, Sep 2009]

ZFP57 Gene-Disease associations (from GenCC):

diabetes mellitus, transient neonatal, 1
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
transient neonatal diabetes mellitus
Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

ZFP57 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 6-29672244-T-C is Benign according to our data. Variant chr6-29672244-T-C is described in ClinVar as Benign. ClinVar VariationId is 1290020.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOG	NM_206809.4 link	c.*1059T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000376917.8	NP_996532.2	Q16653-1
ZFP57	NM_001109809.5 link	c.*256A>G		downstream_gene_variant		ENST00000376883.2	NP_001103279.2	Q9NU63-3A0A1U9X8V5B7ZW61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOG	ENST00000376917.8 link	c.*1059T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_206809.4	ENSP00000366115.3		Q16653-1
ZFP57	ENST00000376883.2 link	c.*256A>G		downstream_gene_variant		5	NM_001109809.5	ENSP00000366080.2		Q9NU63-3

Frequencies

GnomAD3 genomes

AF:

0.878

AC:

132880

AN:

151306

Hom.:

58809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.956

Gnomad AMI

AF:

0.847

Gnomad AMR

AF:

0.915

Gnomad ASJ

AF:

0.898

Gnomad EAS

AF:

0.986

Gnomad SAS

AF:

0.935

Gnomad FIN

AF:

0.691

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.838

Gnomad OTH

AF:

0.892

GnomAD4 exome

AF:

0.847

AC:

8212

AN:

9696

Hom.:

3505

Cov.:

AF XY:

0.844

AC XY:

4933

AN XY:

5844

show subpopulations

African (AFR)

AF:

0.944

AC:

302

AN:

320

American (AMR)

AF:

0.940

AC:

220

AN:

234

Ashkenazi Jewish (ASJ)

AF:

0.862

AC:

262

AN:

304

East Asian (EAS)

AF:

0.995

AC:

575

AN:

578

South Asian (SAS)

AF:

0.884

AC:

122

AN:

138

European-Finnish (FIN)

AF:

0.665

AC:

125

AN:

188

Middle Eastern (MID)

AF:

0.860

AC:

AN:

European-Non Finnish (NFE)

AF:

0.831

AC:

6124

AN:

7368

Other (OTH)

AF:

0.851

AC:

439

AN:

516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

130

195

260

325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.878

AC:

133003

AN:

151420

Hom.:

58874

Cov.:

AF XY:

0.874

AC XY:

64628

AN XY:

73920

show subpopulations

African (AFR)

AF:

0.956

AC:

39449

AN:

41268

American (AMR)

AF:

0.915

AC:

13905

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.898

AC:

3113

AN:

3466

East Asian (EAS)

AF:

0.986

AC:

5077

AN:

5148

South Asian (SAS)

AF:

0.936

AC:

4500

AN:

4808

European-Finnish (FIN)

AF:

0.691

AC:

7160

AN:

10362

Middle Eastern (MID)

AF:

0.887

AC:

259

AN:

292

European-Non Finnish (NFE)

AF:

0.838

AC:

56913

AN:

67890

Other (OTH)

AF:

0.893

AC:

1856

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

730

1459

2189

2918

3648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.858

Hom.:

6973

Bravo

AF:

0.899

Asia WGS

AF:

0.956

AC:

3324

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.43

(source)

DANN

Benign

0.27

PhyloP100

-3.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over