rs61730328

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001109809.5(ZFP57):c.783C>T(p.Cys261=) 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

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 -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 [Likely_benign]. Clinvar id is 130772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-29673328-G-A is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 803 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP57	NM_001109809.5 linkuse as main transcript	c.783C>T	p.Cys261=	synonymous_variant	5/5	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2 linkuse as main transcript	c.567C>T	p.Cys189=	synonymous_variant	4/4		NP_001353262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP57	ENST00000376883.2 linkuse as main transcript	c.783C>T	p.Cys261=	synonymous_variant	5/5	5	NM_001109809.5	ENSP00000366080	P1	Q9NU63-3
ZFP57	ENST00000488757.6 linkuse as main transcript	c.567C>T	p.Cys189=	synonymous_variant	4/4	1		ENSP00000418259

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

GnomAD3 exomes

AF:

0.00360

AC:

881

AN:

244652

Hom.:

AF XY:

0.00364

AC XY:

487

AN XY:

133894

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 SAS exome

AF:

0.00135

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

Gnomad4 AFR exome

AF:

0.00917

Gnomad4 AMR exome

AF:

0.00445

Gnomad4 ASJ exome

AF:

0.0153

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00152

Gnomad4 FIN exome

AF:

0.000325

Gnomad4 NFE exome

AF:

0.00320

Gnomad4 OTH exome

AF:

0.00444

GnomAD4 genome

AF:

0.00527

AC:

803

AN:

152276

Hom.:

Cov.:

AF XY:

0.00508

AC XY:

378

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00951

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00376

Gnomad4 OTH

AF:

0.00806

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

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	ZFP57: BP4, BP7, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Diabetes mellitus, transient neonatal, 1

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 16, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	May 19, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 21, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.7

DANN

Benign

0.86

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