rs587780516

chr6-29673518-T-CchrNT_113891.3-1159990-T-CchrNT_167245.2-939063-T-CchrNT_167246.2-938631-T-CchrNT_167247.2-938891-T-CchrNT_167248.2-939018-T-CchrNT_167249.2-982549-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001109809.5(ZFP57):c.593A>G(p.Asn198Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,613,052 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 101 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 82 hom. )

Consequence

ZFP57
NM_001109809.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.993

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022326708).

BP6

Variant 6-29673518-T-C is Benign according to our data. Variant chr6-29673518-T-C is described in ClinVar as [Benign]. Clinvar id is 130771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-29673518-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFP57	NM_001109809.5 linkuse as main transcript	c.593A>G	p.Asn198Ser	missense_variant	5/5	ENST00000376883.2
ZFP57	NM_001366333.2 linkuse as main transcript	c.377A>G	p.Asn126Ser	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP57	ENST00000376883.2 linkuse as main transcript	c.593A>G	p.Asn198Ser	missense_variant	5/5	5	NM_001109809.5	P1	Q9NU63-3
ZFP57	ENST00000488757.6 linkuse as main transcript	c.377A>G	p.Asn126Ser	missense_variant	4/4	1

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2909

AN:

152168

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0662

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00792

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00509

AC:

1246

AN:

244666

Hom.:

AF XY:

0.00412

AC XY:

552

AN XY:

133896

show subpopulations

Gnomad AFR exome

AF:

0.0708

Gnomad AMR exome

AF:

0.00462

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00168

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000109

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.00222

AC:

3239

AN:

1460766

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

1425

AN XY:

726698

show subpopulations

Gnomad4 AFR exome

AF:

0.0725

Gnomad4 AMR exome

AF:

0.00568

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00204

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000890

Gnomad4 OTH exome

AF:

0.00432

GnomAD4 genome

AF:

0.0192

AC:

2920

AN:

152286

Hom.:

101

Cov.:

AF XY:

0.0193

AC XY:

1438

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0663

Gnomad4 AMR

AF:

0.00791

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00390

Hom.:

Bravo

AF:

0.0222

ESP6500AA

AF:

0.0611

AC:

159

ESP6500EA

AF:

0.000195

AC:

ExAC

AF:

0.00576

AC:

672

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Diabetes mellitus, transient neonatal, 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 28, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 18, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 05, 2013

- -

Monogenic diabetes

Benign:1

Benign, criteria provided, single submitter

research

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Nov 21, 2018

ACMG criteria: BP4 (REVEL 0.013 + 9 predictors), BS2 (59 homozygotes in gnomAD), BA1 (7% MAF in gnomAD African population)= benign -

ZFP57-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 08, 2019

This variant is classified as 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

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.84

Cadd

Benign

0.019

Dann

Benign

0.38

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.59

T;T;T

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.39

N;N;.

REVEL

Benign

0.013

Sift

Benign

0.77

T;T;.

Sift4G

Benign

0.70

T;T;T

Polyphen

0.11

B;B;.

Vest4

0.022

MVP

0.15

MPC

0.34

ClinPred

0.0022

GERP RS

-2.3

Varity_R

0.024

gMVP

0.027

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over