Variant chr19-15424838-C-T 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_001371589.1(WIZ):c.5089G>A(p.Gly1697Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,610,608 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

WIZ
NM_001371589.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

Variant links:

Genes affected

WIZ (HGNC:30917): (WIZ zinc finger) Enables several functions, including DNA-binding transcription factor activity, RNA polymerase II-specific; histone methyltransferase binding activity; and transcription corepressor binding activity. Involved in positive regulation of nuclear cell cycle DNA replication and protein stabilization. Located in midbody and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

WIZ 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=0.015037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WIZ	NM_001371589.1 linkuse as main transcript	c.5089G>A	p.Gly1697Ser	missense_variant	11/13	ENST00000673675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIZ	ENST00000673675.1 linkuse as main transcript	c.5089G>A	p.Gly1697Ser	missense_variant	11/13		NM_001371589.1	P1

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000334

AC:

AN:

236562

Hom.:

AF XY:

0.000354

AC XY:

AN XY:

129862

show subpopulations

Gnomad AFR exome

AF:

0.0000712

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.000114

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000228

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000241

AC:

352

AN:

1458284

Hom.:

Cov.:

AF XY:

0.000263

AC XY:

191

AN XY:

725226

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000450

Gnomad4 ASJ exome

AF:

0.00527

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000257

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000150

Gnomad4 OTH exome

AF:

0.000349

GnomAD4 genome

AF:

0.000269

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000433

Hom.:

Bravo

AF:

0.000261

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000248

AC:

ExAC

AF:

0.000258

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

Aug 17, 2022

The c.1804G>A (p.G602S) alteration is located in exon 6 (coding exon 5) of the WIZ gene. This alteration results from a G to A substitution at nucleotide position 1804, causing the glycine (G) at amino acid position 602 to be replaced by a serine (S). 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

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

.;T;.;T;.;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.90

D;D;D;D;D;D

M_CAP

Benign

0.0058

MetaRNN

Benign

0.015

T;T;T;T;T;T

MetaSVM

Benign

-0.86

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.2

N;.;N;.;.;.

REVEL

Benign

0.18

Sift

Benign

0.041

D;.;D;.;.;.

Sift4G

Benign

0.27

T;T;T;T;T;.

Polyphen

1.0

D;.;.;.;.;.

Vest4

0.62

MVP

0.38

MPC

1.3

ClinPred

0.069

GERP RS

5.6

gMVP

0.77

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