rs61730328

Variant names:

• chr6-29673328-G-A
• rs61730328
• NM_001109809.5:c.783C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-29673328-G-A
• chr6-29673328-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001109809.5(ZFP57):​c.783C>T​(p.Cys261Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,613,048 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (22 hom.)
• Consequence: ZFP57 NM_001109809.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.78
• Publications: 4 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• narcolepsy 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-29673328-G-A is Benign according to our data. Variant chr6-29673328-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 130772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.78 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00527 (803/152276) while in subpopulation AFR AF = 0.00951 (395/41552). AF 95% confidence interval is 0.00873. There are 3 homozygotes in GnomAd4. There are 378 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109809.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP57	NM_001109809.5	MANE Select	c.783C>T	p.Cys261Cys	synonymous	Exon 5 of 5	NP_001103279.2	Q9NU63-3
	ZFP57	NM_001366333.2		c.567C>T	p.Cys189Cys	synonymous	Exon 4 of 4	NP_001353262.1	A0A7I2S1M6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP57	ENST00000376883.2	TSL:5 MANE Select	c.783C>T	p.Cys261Cys	synonymous	Exon 5 of 5	ENSP00000366080.2	Q9NU63-3
	ZFP57	ENST00000488757.6	TSL:1	c.567C>T	p.Cys189Cys	synonymous	Exon 4 of 4	ENSP00000418259.2	A0A7I2S1M6
	ZFP57	ENST00000931172.1		c.783C>T	p.Cys261Cys	synonymous	Exon 4 of 4	ENSP00000601231.1

Frequencies

GnomAD3 genomes AF: 0.00522 AC: 795 AN: 152158 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00934

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00376

Gnomad OTH AF: 0.00814

GnomAD2 exomes AF: 0.00360 AC: 881 AN: 244652 AF XY: 0.00364

Gnomad AFR exome AF: 0.00844

Gnomad AMR exome AF: 0.00389

Gnomad ASJ exome AF: 0.0151

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000418

Gnomad NFE exome AF: 0.00369

Gnomad OTH exome AF: 0.00333

GnomAD4 exome AF: 0.00337 AC: 4923 AN: 1460772 Hom.: 22 Cov.: 31 AF XY: 0.00338 AC XY: 2459 AN XY: 726702

African (AFR) AF: 0.00917 AC: 307 AN: 33480

American (AMR) AF: 0.00445 AC: 199 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 400 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00152 AC: 131 AN: 86258

European-Finnish (FIN) AF: 0.000325 AC: 17 AN: 52310

Middle Eastern (MID) AF: 0.00763 AC: 44 AN: 5768

European-Non Finnish (NFE) AF: 0.00320 AC: 3555 AN: 1112010

Other (OTH) AF: 0.00444 AC: 268 AN: 60386

GnomAD4 genome AF: 0.00527 AC: 803 AN: 152276 Hom.: 3 Cov.: 32 AF XY: 0.00508 AC XY: 378 AN XY: 74460

African (AFR) AF: 0.00951 AC: 395 AN: 41552

American (AMR) AF: 0.00471 AC: 72 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4832

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00376 AC: 256 AN: 68026

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.00547 Hom.: 3

Bravo AF: 0.00589

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00409

EpiControl AF: 0.00498

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	3	Diabetes mellitus, transient neonatal, 1 (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.7
DANN	Benign	0.86
PhyloP100		1.8
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs61730328; hg19: chr6-29641105;