rs3135049

Variant names:

• chr6-29672244-T-C
• rs3135049
• ENST00000376889.3:n.*1425T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.52
• Publications: 4 publications found

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]

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

ACMG classification

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	c.*1059T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000376917.8	NP_996532.2
ZFP57	NM_001109809.5	c.*256A>G		downstream_gene_variant		ENST00000376883.2	NP_001103279.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.878 AC: 132880 AN: 151306 Hom.: 58809 Cov.: 27

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.: 2 AF XY: 0.844 AC XY: 4933 AN XY: 5844

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: 43 AN: 50

European-Non Finnish (NFE) AF: 0.831 AC: 6124 AN: 7368

Other (OTH) AF: 0.851 AC: 439 AN: 516

GnomAD4 genome AF: 0.878 AC: 133003 AN: 151420 Hom.: 58874 Cov.: 27 AF XY: 0.874 AC XY: 64628 AN XY: 73920

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

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

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
DANN	Benign	0.27
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3135049; hg19: chr6-29640021;