Variant chr18-58919044-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001375912.1(ZNF532):c.757C>G(p.Leu253Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,613,924 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 16 hom. )

Consequence

ZNF532
NM_001375912.1 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.733

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032782257).

BP6

Variant 18-58919044-C-G is Benign according to our data. Variant chr18-58919044-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 773073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0011 (1613/1461656) while in subpopulation MID AF= 0.0303 (175/5768). AF 95% confidence interval is 0.0267. There are 16 homozygotes in gnomad4_exome. There are 822 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 176 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF532	NM_001375912.1 link	c.757C>G	p.Leu253Val	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.757C>G	p.Leu253Val	missense_variant	3/10	1	NM_001375912.1	ENSP00000468238.1		Q9HCE3

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

176

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00181

AC:

454

AN:

250190

Hom.:

AF XY:

0.00194

AC XY:

262

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.0233

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000360

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.00491

GnomAD4 exome

AF:

0.00110

AC:

1613

AN:

1461656

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

822

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.0216

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000523

Gnomad4 OTH exome

AF:

0.00298

GnomAD4 genome

AF:

0.00116

AC:

176

AN:

152268

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00478

Hom.:

Bravo

AF:

0.00155

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00163

AC:

198

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00207

EpiControl

AF:

0.00190

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.4

DANN

Benign

0.45

DEOGEN2

Benign

0.0085

T;T;T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.67

.;.;.;.;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.0033

T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.6

L;L;L;L;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.060

N;.;.;.;.

REVEL

Benign

0.044

Sift

Benign

0.91

T;.;.;.;.

Sift4G

Benign

0.56

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.034

MVP

0.068

MPC

0.55

ClinPred

0.0055

GERP RS

1.0

Varity_R

0.089

gMVP

0.024

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