Variant chr16-71448551-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001381984.1(ZNF23):c.1603C>G(p.Leu535Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,058 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZNF23
NM_001381984.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.250

Variant links:

Genes affected

ZNF23 (HGNC:13023): (zinc finger protein 23) Enables sequence-specific double-stranded 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]

ZNF23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04100153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF23	NM_001381984.1 linkuse as main transcript	c.1603C>G	p.Leu535Val	missense_variant	5/5	ENST00000647773.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF23	ENST00000647773.2 linkuse as main transcript	c.1603C>G	p.Leu535Val	missense_variant	5/5		NM_001381984.1	P1

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151068

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251422

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135884

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727234

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151192

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73872

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:

0.0000148

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Mar 24, 2023

The c.1474C>G (p.L492V) alteration is located in exon 6 (coding exon 3) of the ZNF23 gene. This alteration results from a C to G substitution at nucleotide position 1474, causing the leucine (L) at amino acid position 492 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.7

DANN

Uncertain

0.99

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.000030

LIST_S2

Benign

0.43

T;T;.;.;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.041

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Uncertain

0.50

Sift4G

Benign

0.38

T;.;T;T;T

Polyphen

0.91

.;.;P;P;P

Vest4

0.14

MutPred

0.26

.;.;Loss of catalytic residue at L492 (P = 0.031);Loss of catalytic residue at L492 (P = 0.031);Loss of catalytic residue at L492 (P = 0.031);

MVP

0.19

MPC

0.088

ClinPred

0.086

GERP RS

3.3

Varity_R

0.023

gMVP

0.046

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