19-42224684-T-C

Position:

chr19-42224684-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_133444.3(ZNF526):c.281T>C(p.Val94Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,614,138 control chromosomes in the GnomAD database, including 9,141 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.079 ( 663 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8478 hom. )

Consequence

ZNF526
NM_133444.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: -0.367

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.889007E-4).

BP6

Variant 19-42224684-T-C is Benign according to our data. Variant chr19-42224684-T-C is described in ClinVar as [Benign]. Clinvar id is 130837.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-42224684-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF526	NM_133444.3 linkuse as main transcript	c.281T>C	p.Val94Ala	missense_variant	3/3	ENST00000301215.8
ZNF526	NM_001314033.3 linkuse as main transcript	c.281T>C	p.Val94Ala	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF526	ENST00000301215.8 linkuse as main transcript	c.281T>C	p.Val94Ala	missense_variant	3/3	1	NM_133444.3	P1
ZNF526	ENST00000710326.1 linkuse as main transcript	c.281T>C	p.Val94Ala	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes

AF:

0.0791

AC:

12042

AN:

152156

Hom.:

665

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0999

Gnomad EAS

AF:

0.0903

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.0506

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.0966

GnomAD3 exomes

AF:

0.109

AC:

27336

AN:

251264

Hom.:

1738

AF XY:

0.114

AC XY:

15414

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.100

Gnomad EAS exome

AF:

0.0947

Gnomad SAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.0527

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.103

AC:

150203

AN:

1461864

Hom.:

8478

Cov.:

AF XY:

0.106

AC XY:

76757

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0177

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.0737

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.0524

Gnomad4 NFE exome

AF:

0.100

Gnomad4 OTH exome

AF:

0.106

GnomAD4 genome

AF:

0.0790

AC:

12029

AN:

152274

Hom.:

663

Cov.:

AF XY:

0.0791

AC XY:

5887

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0213

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.0999

Gnomad4 EAS

AF:

0.0897

Gnomad4 SAS

AF:

0.178

Gnomad4 FIN

AF:

0.0506

Gnomad4 NFE

AF:

0.101

Gnomad4 OTH

AF:

0.0946

Alfa

AF:

0.0980

Hom.:

1251

Bravo

AF:

0.0813

TwinsUK

AF:

0.0979

AC:

363

ALSPAC

AF:

0.0950

AC:

366

ESP6500AA

AF:

0.0177

AC:

ESP6500EA

AF:

0.101

AC:

865

ExAC

AF:

0.109

AC:

13276

Asia WGS

AF:

0.133

AC:

462

AN:

3478

EpiCase

AF:

0.109

EpiControl

AF:

0.108

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

ZNF526-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.040

DANN

Benign

0.30

DEOGEN2

Benign

0.0079

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.18

MetaRNN

Benign

0.00099

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

0.17

REVEL

Benign

0.037

Sift

Benign

0.76

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.015

MPC

0.37

ClinPred

0.00087

GERP RS

1.7

Varity_R

0.020

gMVP

0.11

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