Variant 19-36950456-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198539.4(ZNF568):c.1303G>A(p.Val435Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,612,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ZNF568
NM_198539.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.98

Variant links:

Genes affected

ZNF568 (HGNC:25392): (zinc finger protein 568) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in embryonic placenta morphogenesis and negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF568 links:

ENSG00000291239 (HGNC:):

ENSG00000291239 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.117724866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF568	NM_198539.4 link	c.1303G>A	p.Val435Ile	missense_variant	7/7	ENST00000333987.12	NP_940941.2	Q3ZCX4-1Q96AZ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF568	ENST00000333987.12 link	c.1303G>A	p.Val435Ile	missense_variant	7/7	1	NM_198539.4	ENSP00000334685.7		Q3ZCX4-1
ENSG00000291239	ENST00000706165.1 link	c.358+13214G>A		intron_variant				ENSP00000516244.1		C9JLX5

Frequencies

GnomAD3 genomes

AF:

0.0000662

AC:

AN:

151102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

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:

0.000118

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.000120

AC:

AN:

250122

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135558

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000141

AC:

206

AN:

1460998

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

103

AN XY:

726824

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000151

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.0000662

AC:

AN:

151102

Hom.:

Cov.:

AF XY:

0.0000542

AC XY:

AN XY:

73744

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000659

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000483

Alfa

AF:

0.000118

Hom.:

Bravo

AF:

0.000166

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.1303G>A (p.V435I) alteration is located in exon 7 (coding exon 5) of the ZNF568 gene. This alteration results from a G to A substitution at nucleotide position 1303, causing the valine (V) at amino acid position 435 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0012

T;.;.;T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.099

.;T;T;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.47

N;.;.;N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.46

N;N;.;.;.

REVEL

Benign

0.058

Sift

Benign

0.26

T;T;.;.;.

Sift4G

Benign

0.22

T;T;T;T;T

Polyphen

0.94

P;.;.;P;.

Vest4

0.043

MVP

0.42

MPC

0.67

ClinPred

0.047

GERP RS

1.9

Varity_R

0.034

gMVP

0.030

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