chr6-29673008-T-A

Position:

chr6-29673008-T-A

Variant summary

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

The NM_001109809.5(ZFP57):c.1103A>T(p.Asp368Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,612,974 control chromosomes in the GnomAD database, including 994 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 414 hom., cov: 32)

Exomes 𝑓: 0.019 ( 580 hom. )

Consequence

ZFP57
NM_001109809.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.263

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=0.0017012954).

BP6

Variant 6-29673008-T-A is Benign according to our data. Variant chr6-29673008-T-A is described in ClinVar as [Benign]. Clinvar id is 130773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-29673008-T-A is described in Lovd as [Benign]. Variant chr6-29673008-T-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 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.1103A>T	p.Asp368Val	missense_variant	5/5	ENST00000376883.2
ZFP57	NM_001366333.2 linkuse as main transcript	c.887A>T	p.Asp296Val	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP57	ENST00000376883.2 linkuse as main transcript	c.1103A>T	p.Asp368Val	missense_variant	5/5	5	NM_001109809.5	P1	Q9NU63-3
ZFP57	ENST00000488757.6 linkuse as main transcript	c.887A>T	p.Asp296Val	missense_variant	4/4	1

Frequencies

GnomAD3 genomes

AF:

0.0508

AC:

7729

AN:

152084

Hom.:

413

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0345

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0188

Gnomad OTH

AF:

0.0569

GnomAD3 exomes

AF:

0.0221

AC:

5416

AN:

244662

Hom.:

193

AF XY:

0.0200

AC XY:

2677

AN XY:

133898

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.0213

Gnomad ASJ exome

AF:

0.0267

Gnomad EAS exome

AF:

0.000168

Gnomad SAS exome

AF:

0.00761

Gnomad FIN exome

AF:

0.00209

Gnomad NFE exome

AF:

0.0178

Gnomad OTH exome

AF:

0.0257

GnomAD4 exome

AF:

0.0192

AC:

28107

AN:

1460772

Hom.:

580

Cov.:

AF XY:

0.0185

AC XY:

13410

AN XY:

726702

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.0240

Gnomad4 ASJ exome

AF:

0.0248

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.00774

Gnomad4 FIN exome

AF:

0.00275

Gnomad4 NFE exome

AF:

0.0174

Gnomad4 OTH exome

AF:

0.0227

GnomAD4 genome

AF:

0.0508

AC:

7731

AN:

152202

Hom.:

414

Cov.:

AF XY:

0.0482

AC XY:

3590

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.0343

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.0188

Gnomad4 OTH

AF:

0.0559

Alfa

AF:

0.0187

Hom.:

Bravo

AF:

0.0585

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.0166

AC:

ESP6500AA

AF:

0.125

AC:

311

ESP6500EA

AF:

0.0196

AC:

100

ExAC

AF:

0.0237

AC:

2768

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0205

EpiControl

AF:

0.0228

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Diabetes mellitus, transient neonatal, 1

Benign:1

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.31

.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.52

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.9

D;D;.

REVEL

Benign

0.013

Sift

Benign

0.062

T;D;.

Sift4G

Benign

0.12

T;T;T

Polyphen

0.11

B;B;.

Vest4

0.12

MPC

1.2

ClinPred

0.031

GERP RS

-1.4

Varity_R

0.048

gMVP

0.20

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