Genetic Variant ZNF528:p.Ala28Val (chr19-52405974-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032423.3(ZNF528):c.83C>T(p.Ala28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,612,022 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 6 hom. )

Consequence

ZNF528
NM_032423.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.706

Variant links:

Genes affected

ZNF528 (HGNC:29384): (zinc finger protein 528) 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]

ZNF528 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015334696).

BP6

Variant 19-52405974-C-T is Benign according to our data. Variant chr19-52405974-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 782628.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF528	NM_032423.3 link	c.83C>T	p.Ala28Val	missense_variant	Exon 5 of 7	ENST00000360465.8	NP_115799.2	Q3MIS6-1
ZNF528	XM_006723418.3 link	c.83C>T	p.Ala28Val	missense_variant	Exon 4 of 8		XP_006723481.1
ZNF528	XM_047439511.1 link	c.53C>T	p.Ala18Val	missense_variant	Exon 2 of 6		XP_047295467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF528	ENST00000360465.8 link	c.83C>T	p.Ala28Val	missense_variant	Exon 5 of 7	1	NM_032423.3	ENSP00000353652.3		Q3MIS6-1

Frequencies

GnomAD3 genomes

AF:

0.00200

AC:

305

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00291

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00200

AC:

503

AN:

251422

Hom.:

AF XY:

0.00219

AC XY:

297

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00208

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00261

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00280

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00277

AC:

4042

AN:

1459750

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

2024

AN XY:

726146

show subpopulations

Gnomad4 AFR exome

AF:

0.000449

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00286

Gnomad4 FIN exome

AF:

0.000470

Gnomad4 NFE exome

AF:

0.00318

Gnomad4 OTH exome

AF:

0.00232

GnomAD4 genome

AF:

0.00200

AC:

305

AN:

152272

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00291

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00212

Hom.:

Bravo

AF:

0.00210

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00208

AC:

253

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00267

EpiControl

AF:

0.00338

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 07, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

.;T;T;T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.056

T;T;T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.015

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

.;.;L;.;.

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.4

N;N;D;.;.

REVEL

Benign

0.10

Sift

Benign

0.22

T;T;T;.;.

Sift4G

Uncertain

0.029

D;D;T;D;D

Polyphen

0.81

.;.;P;.;.

Vest4

0.21

MVP

0.33

MPC

0.058

ClinPred

0.016

GERP RS

2.1

Varity_R

0.058

gMVP

0.047

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