rs587780515

Positions:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP3BP6BA1

The NM_001109809.5(ZFP57):c.113G>A(p.Arg38Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,614,102 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R38W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0013 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 141 hom. )

Consequence

ZFP57
NM_001109809.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.00300

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 -8 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 6-29676891-C-T is Benign according to our data. Variant chr6-29676891-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 130770.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}. Variant chr6-29676891-C-T is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0591 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.113G>A	p.Arg38Gln	missense_variant	2/5	ENST00000376883.2
ZFP57	NM_001366333.2 linkuse as main transcript	c.-93-832G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP57	ENST00000376883.2 linkuse as main transcript	c.113G>A	p.Arg38Gln	missense_variant	2/5	5	NM_001109809.5	P1	Q9NU63-3
ZFP57	ENST00000488757.6 linkuse as main transcript	c.-93-832G>A		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

202

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0252

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00107

AC:

267

AN:

249380

Hom.:

AF XY:

0.00113

AC XY:

153

AN XY:

135332

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00623

Gnomad SAS exome

AF:

0.00274

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000407

Gnomad OTH exome

AF:

0.000989

GnomAD4 exome

AF:

0.00216

AC:

3154

AN:

1461786

Hom.:

141

Cov.:

AF XY:

0.00224

AC XY:

1628

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0612

Gnomad4 SAS exome

AF:

0.00278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000299

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00132

AC:

201

AN:

152316

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0253

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000666

Hom.:

Bravo

AF:

0.000514

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00138

AC:

167

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.00101

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 26, 2023	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Nov 04, 2013	- -

Diabetes mellitus, transient neonatal, 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.0036

T;T

MetaSVM

Benign

-0.90

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.30

N;N

REVEL

Benign

0.058

Sift

Benign

0.34

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0010

B;B

Vest4

0.25

MVP

0.16

MPC

0.51

ClinPred

0.012

GERP RS

2.3

gMVP

0.025

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.61

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.61

Position offset: -1

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