Variant rs776086354 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_133444.3(ZNF526):c.1672C>T(p.Arg558Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,454,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ZNF526
NM_133444.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.594

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:

ENSG00000288671 (HGNC:):

ENSG00000288671 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=0.14890447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF526	NM_133444.3 linkuse as main transcript	c.1672C>T	p.Arg558Cys	missense_variant	3/3	ENST00000301215.8	NP_597701.1	Q8TF50H9ZYJ3
ZNF526	NM_001314033.3 linkuse as main transcript	c.1672C>T	p.Arg558Cys	missense_variant	3/3		NP_001300962.1	Q8TF50H9ZYJ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF526	ENST00000301215.8 linkuse as main transcript	c.1672C>T	p.Arg558Cys	missense_variant	3/3	1	NM_133444.3	ENSP00000301215.2	Q8TF50
ENSG00000288671	ENST00000678490.1 linkuse as main transcript	c.91+5982G>A		intron_variant				ENSP00000502878.1	A0A7I2V2F5
ZNF526	ENST00000710326.1 linkuse as main transcript	c.1672C>T	p.Arg558Cys	missense_variant	3/3			ENSP00000518206.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244446

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1454880

Hom.:

Cov.:

AF XY:

0.00000967

AC XY:

AN XY:

724090

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 26, 2015

- -

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.1672C>T (p.R558C) alteration is located in exon 3 (coding exon 1) of the ZNF526 gene. This alteration results from a C to T substitution at nucleotide position 1672, causing the arginine (R) at amino acid position 558 to be replaced by a cysteine (C). 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

Pathogenic

0.57

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.017

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.79

M_CAP

Benign

0.013

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.62

REVEL

Benign

0.19

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Polyphen

0.76

Vest4

0.32

MutPred

0.48

Loss of MoRF binding (P = 0.0128);

MVP

0.23

MPC

1.2

ClinPred

0.49

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.33

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