rs61730328

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.78

Publications

4 publications found

Variant links:

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]

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 -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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP57	NM_001109809.5 link	c.783C>T	p.Cys261Cys	synonymous_variant	Exon 5 of 5	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2 link	c.567C>T	p.Cys189Cys	synonymous_variant	Exon 4 of 4		NP_001353262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP57	ENST00000376883.2 link	c.783C>T	p.Cys261Cys	synonymous_variant	Exon 5 of 5	5	NM_001109809.5	ENSP00000366080.2
ZFP57	ENST00000488757.6 link	c.567C>T	p.Cys189Cys	synonymous_variant	Exon 4 of 4	1		ENSP00000418259.2

Frequencies

GnomAD3 genomes

AF:

0.00522

AC:

795

AN:

152158

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.00338

AC XY:

2459

AN XY:

726702

show subpopulations

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:

AN:

39700

South Asian (SAS)

AF:

0.00152

AC:

131

AN:

86258

European-Finnish (FIN)

AF:

0.000325

AC:

AN:

52310

Middle Eastern (MID)

AF:

0.00763

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00320

AC:

3555

AN:

1112010

Other (OTH)

AF:

0.00444

AC:

268

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

382

764

1146

1528

1910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

272

408

544

680

<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:

0.00527

AC:

803

AN:

152276

Hom.:

Cov.:

AF XY:

0.00508

AC XY:

378

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00951

AC:

395

AN:

41552

American (AMR)

AF:

0.00471

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00145

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00376

AC:

256

AN:

68026

Other (OTH)

AF:

0.00806

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

133

177

221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00547

Hom.:

Bravo

AF:

0.00589

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00409

EpiControl

AF:

0.00498

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ZFP57: BP4, BP7, BS2 -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diabetes mellitus, transient neonatal, 1

Benign:3

Aug 16, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 19, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not specified

Benign:1

Feb 21, 2013

Genetic Services Laboratory, University of Chicago

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

-0.79

CADD

Benign

4.7

(source)

DANN

Benign

0.86

PhyloP100

1.8

Mutation Taster

=98/2

polymorphism

(source)

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

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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