Variant chr19-56414048-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152478.3(ZNF583):c.99A>C(p.Lys33Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 1,607,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

ZNF583
NM_152478.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -8.45

Variant links:

Genes affected

ZNF583 (HGNC:26427): (zinc finger protein 583) 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 regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF583 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046761543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF583	NM_152478.3 linkuse as main transcript	c.99A>C	p.Lys33Asn	missense_variant	3/5	ENST00000333201.13	NP_689691.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF583	ENST00000333201.13 linkuse as main transcript	c.99A>C	p.Lys33Asn	missense_variant	3/5	2	NM_152478.3	ENSP00000388502	P1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152224

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000165

AC:

AN:

242552

Hom.:

AF XY:

0.000183

AC XY:

AN XY:

131156

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.0000912

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.000274

AC:

399

AN:

1455286

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

185

AN XY:

723954

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

Gnomad4 AMR exome

AF:

0.0000920

Gnomad4 ASJ exome

AF:

0.0000391

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000344

Gnomad4 OTH exome

AF:

0.000167

GnomAD4 genome

AF:

0.000171

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74380

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:

0.0000941

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000249

Hom.:

Bravo

AF:

0.000155

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000140

AC:

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 08, 2022

The c.99A>C (p.K33N) alteration is located in exon 3 (coding exon 2) of the ZNF583 gene. This alteration results from a A to C substitution at nucleotide position 99, causing the lysine (K) at amino acid position 33 to be replaced by an asparagine (N). 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

0.17

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.042

DANN

Benign

0.95

DEOGEN2

Benign

0.019

.;T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.047

T;T;.;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.047

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.79

.;N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.20

N;N;N;N

REVEL

Benign

0.044

Sift

Benign

0.19

T;T;T;T

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.22, 0.22

MutPred

0.54

Loss of methylation at K33 (P = 0.0049);Loss of methylation at K33 (P = 0.0049);Loss of methylation at K33 (P = 0.0049);Loss of methylation at K33 (P = 0.0049);

MVP

0.25

MPC

0.78

ClinPred

0.027

GERP RS

-9.2

Varity_R

0.049

gMVP

0.37

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