Variant 19-42224969-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_133444.3(ZNF526):c.566C>T(p.Pro189Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,614,236 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 5 hom., cov: 32)

Exomes 𝑓: 0.012 ( 134 hom. )

Consequence

ZNF526
NM_133444.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.94

Variant links:

Genes affected

ZNF526 (HGNC:29415): (zinc finger protein 526) 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]

ZNF526 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039301217).

BP6

Variant 19-42224969-C-T is Benign according to our data. Variant chr19-42224969-C-T is described in ClinVar as [Benign]. Clinvar id is 130838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF526	NM_133444.3 linkuse as main transcript	c.566C>T	p.Pro189Leu	missense_variant	3/3	ENST00000301215.8
ZNF526	NM_001314033.3 linkuse as main transcript	c.566C>T	p.Pro189Leu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF526	ENST00000301215.8 linkuse as main transcript	c.566C>T	p.Pro189Leu	missense_variant	3/3	1	NM_133444.3	P1
ZNF526	ENST00000710326.1 linkuse as main transcript	c.566C>T	p.Pro189Leu	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes

AF:

0.00738

AC:

1123

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00725

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0130

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00780

AC:

1961

AN:

251404

Hom.:

AF XY:

0.00785

AC XY:

1066

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00310

Gnomad FIN exome

AF:

0.00698

Gnomad NFE exome

AF:

0.0136

Gnomad OTH exome

AF:

0.00749

GnomAD4 exome

AF:

0.0121

AC:

17714

AN:

1461894

Hom.:

134

Cov.:

AF XY:

0.0118

AC XY:

8564

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.00279

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00312

Gnomad4 FIN exome

AF:

0.00822

Gnomad4 NFE exome

AF:

0.0146

Gnomad4 OTH exome

AF:

0.00988

GnomAD4 genome

AF:

0.00737

AC:

1123

AN:

152342

Hom.:

Cov.:

AF XY:

0.00677

AC XY:

504

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00393

Gnomad4 FIN

AF:

0.00725

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.0121

Hom.:

Bravo

AF:

0.00701

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0140

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0144

AC:

124

ExAC

AF:

0.00787

AC:

955

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0130

EpiControl

AF:

0.0127

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 18, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.53

DEOGEN2

Benign

0.0087

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.61

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.020

REVEL

Benign

0.060

Sift

Benign

0.67

Sift4G

Benign

0.13

Polyphen

0.0050

Vest4

0.29

MVP

0.46

MPC

0.35

ClinPred

0.0047

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.038

gMVP

0.34

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