Variant chr18-58919341-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001375912.1(ZNF532):c.1054G>A(p.Ala352Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000949 in 1,614,104 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00098 ( 1 hom. )

Consequence

ZNF532
NM_001375912.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.24

Variant links:

Genes affected

ZNF532 (HGNC:30940): (zinc finger protein 532) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF532 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012980461).

BS2

High AC in GnomAd4 at 102 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF532	NM_001375912.1 link	c.1054G>A	p.Ala352Thr	missense_variant	3/10	ENST00000591808.6	NP_001362841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF532	ENST00000591808.6 link	c.1054G>A	p.Ala352Thr	missense_variant	3/10	1	NM_001375912.1	ENSP00000468238.1		Q9HCE3

Frequencies

GnomAD3 genomes

AF:

0.000657

AC:

100

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000677

AC:

170

AN:

251176

Hom.:

AF XY:

0.000663

AC XY:

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.000433

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00115

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000978

AC:

1429

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000921

AC XY:

670

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00119

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.000670

AC:

102

AN:

152224

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000864

Hom.:

Bravo

AF:

0.000688

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000642

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000533

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.1054G>A (p.A352T) alteration is located in exon 4 (coding exon 1) of the ZNF532 gene. This alteration results from a G to A substitution at nucleotide position 1054, causing the alanine (A) at amino acid position 352 to be replaced by a threonine (T). 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

Benign

0.079

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T;T;T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.0016

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.84

.;.;.;.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;L;L;L

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.87

N;.;.;.;.

REVEL

Benign

0.093

Sift

Benign

0.14

T;.;.;.;.

Sift4G

Benign

0.12

T;T;T;T;T

Polyphen

0.0090

B;B;B;B;B

Vest4

0.044

MVP

0.10

MPC

0.53

ClinPred

0.025

GERP RS

5.0

Varity_R

0.099

gMVP

0.14

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