Variant chr16-71448412-T-G 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_001381984.1(ZNF23):c.1742A>C(p.Glu581Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,878 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: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ZNF23
NM_001381984.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.244

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:

ENSG00000261611 (HGNC:):

ENSG00000261611 links:

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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=0.15637976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF23	NM_001381984.1 linkuse as main transcript	c.1742A>C	p.Glu581Ala	missense_variant	5/5	ENST00000647773.2	NP_001368913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF23	ENST00000647773.2 linkuse as main transcript	c.1742A>C	p.Glu581Ala	missense_variant	5/5		NM_001381984.1	ENSP00000497736.2	A0A3B3ITE4
ENSG00000261611	ENST00000561908.1 linkuse as main transcript	n.*2077A>C		non_coding_transcript_exon_variant	12/12	2		ENSP00000463741.1	J3QLW9
ENSG00000261611	ENST00000561908.1 linkuse as main transcript	n.*2077A>C		3_prime_UTR_variant	12/12	2		ENSP00000463741.1	J3QLW9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727240

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:

0.00000629

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

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

May 22, 2023

The c.1613A>C (p.E538A) alteration is located in exon 6 (coding exon 3) of the ZNF23 gene. This alteration results from a A to C substitution at nucleotide position 1613, causing the glutamic acid (E) at amino acid position 538 to be replaced by an alanine (A). 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

0.23

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.049

.;.;T;T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.00022

LIST_S2

Benign

0.32

T;T;.;.;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.16

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

.;.;L;L;L

MutationTaster

Benign

0.82

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.97

.;.;N;N;.

REVEL

Benign

0.031

Sift

Benign

0.12

.;.;T;T;.

Sift4G

Pathogenic

0.0010

D;.;D;D;D

Polyphen

0.20

.;.;B;B;B

Vest4

0.35

MutPred

0.47

.;.;Loss of ubiquitination at K533 (P = 0.0539);Loss of ubiquitination at K533 (P = 0.0539);Loss of ubiquitination at K533 (P = 0.0539);

MVP

0.43

MPC

0.19

ClinPred

0.26

GERP RS

3.2

Varity_R

0.048

gMVP

0.072

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