Variant rs77625743 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP5BS2

The NM_001109809.5(ZFP57):c.743G>A(p.Arg248His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,920 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

ZFP57
NM_001109809.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -1.68

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 Likely_benign. Variant got -3 ACMG points.

PP5

Variant 6-29673368-C-T is Pathogenic according to our data. Variant chr6-29673368-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 719.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-29673368-C-T is described in Lovd as [Pathogenic].

BS2

High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP57	NM_001109809.5 linkuse as main transcript	c.743G>A	p.Arg248His	missense_variant	5/5	ENST00000376883.2	NP_001103279.2
ZFP57	NM_001366333.2 linkuse as main transcript	c.527G>A	p.Arg176His	missense_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.743G>A	p.Arg248His	missense_variant	5/5	5	NM_001109809.5	ENSP00000366080	P1	Q9NU63-3
ZFP57	ENST00000488757.6 linkuse as main transcript	c.527G>A	p.Arg176His	missense_variant	4/4	1		ENSP00000418259

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000818

AC:

AN:

244640

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133898

show subpopulations

Gnomad AFR exome

AF:

0.0000698

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1460772

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726702

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000191

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000171

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Diabetes mellitus, transient neonatal, 1

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.16

.;.;T

Eigen

Benign

-0.0025

Eigen_PC

Benign

-0.060

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.67

T;T;T

M_CAP

Uncertain

0.27

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.3e-10

A;A;A

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.3

N;D;.

REVEL

Benign

0.13

Sift

Uncertain

0.015

D;D;.

Sift4G

Uncertain

0.022

D;D;D

Polyphen

1.0

D;P;.

Vest4

0.58

MutPred

0.37

Loss of MoRF binding (P = 0.0283);.;.;

MVP

0.43

MPC

1.4

ClinPred

0.95

GERP RS

3.6

Varity_R

0.096

gMVP

0.18

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