Genetic Variant ZNF529:p.His332Asn (chr19-36547564-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020951.5(ZNF529):c.994C>A(p.His332Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ZNF529
NM_020951.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.74

Variant links:

Genes affected

ZNF529 (HGNC:29328): (zinc finger protein 529) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF529 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF529	NM_020951.5 link	c.994C>A	p.His332Asn	missense_variant	Exon 5 of 5	ENST00000591340.6	NP_066002.3	Q6P280

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF529	ENST00000591340.6 link	c.994C>A	p.His332Asn	missense_variant	Exon 5 of 5	1	NM_020951.5	ENSP00000465578.1	Q6P280
ZNF529	ENST00000334116.7 link	c.679C>A	p.His227Asn	missense_variant	Exon 6 of 6	2		ENSP00000334695.7	A0A0C4DFR4
ZNF529	ENST00000452073.2 link	c.199C>A	p.His67Asn	missense_variant	Exon 1 of 2	3		ENSP00000465917.1	K7EL49
ZNF529	ENST00000590656.1 link	c.-36C>A		upstream_gene_variant		3		ENSP00000468594.1	K7ES80

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

249898

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135524

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:

0.0000530

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461602

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000198

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.994C>A (p.H332N) alteration is located in exon 6 (coding exon 4) of the ZNF529 gene. This alteration results from a C to A substitution at nucleotide position 994, causing the histidine (H) at amino acid position 332 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

Pathogenic

0.96

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.20

T;T

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.52

D;D

MetaSVM

Benign

-0.45

MutationAssessor

Pathogenic

3.2

.;M

PrimateAI

Uncertain

0.69

REVEL

Benign

0.25

Sift4G

Pathogenic

0.0

D;D

Vest4

0.44

MVP

0.88

MPC

0.65

ClinPred

0.91

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.30

gMVP

0.097

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