Variant chr11-123726346-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003455.4(ZNF202):c.1598G>C(p.Gly533Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00016 in 1,614,206 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

ZNF202
NM_003455.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

Variant links:

Genes affected

ZNF202 (HGNC:12994): (zinc finger protein 202) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in chromosome; nuclear body; and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF202 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35804135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF202	NM_003455.4 linkuse as main transcript	c.1598G>C	p.Gly533Ala	missense_variant	9/9	ENST00000530393.6	NP_003446.2	O95125-1A0A024R3M3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF202	ENST00000530393.6 linkuse as main transcript	c.1598G>C	p.Gly533Ala	missense_variant	9/9	1	NM_003455.4	ENSP00000432504.1	O95125-1
ZNF202	ENST00000336139.8 linkuse as main transcript	c.1598G>C	p.Gly533Ala	missense_variant	8/8	1		ENSP00000337724.4	O95125-1
ZNF202	ENST00000529691.1 linkuse as main transcript	c.1598G>C	p.Gly533Ala	missense_variant	7/7	2		ENSP00000433881.1	O95125-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000147

AC:

AN:

251478

Hom.:

AF XY:

0.000169

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000165

AC:

241

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

115

AN XY:

727246

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:

0.0000936

Gnomad4 NFE exome

AF:

0.000210

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000112

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000163

Hom.:

Bravo

AF:

0.0000907

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

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

Dec 05, 2024

The c.1598G>C (p.G533A) alteration is located in exon 9 (coding exon 6) of the ZNF202 gene. This alteration results from a G to C substitution at nucleotide position 1598, causing the glycine (G) at amino acid position 533 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.44

T;T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.85

.;.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.9

L;L;L

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Benign

0.17

Sift

Benign

0.17

T;T;T

Sift4G

Uncertain

0.014

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.41

MVP

0.55

MPC

0.23

ClinPred

0.37

GERP RS

4.5

Varity_R

0.29

gMVP

0.17

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