Variant 11-123726266-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_003455.4(ZNF202):c.1678G>A(p.Ala560Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

ZNF202
NM_003455.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.242

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:

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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=0.020681083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF202	NM_003455.4 linkuse as main transcript	c.1678G>A	p.Ala560Thr	missense_variant	9/9	ENST00000530393.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF202	ENST00000530393.6 linkuse as main transcript	c.1678G>A	p.Ala560Thr	missense_variant	9/9	1	NM_003455.4	P1	O95125-1
ZNF202	ENST00000336139.8 linkuse as main transcript	c.1678G>A	p.Ala560Thr	missense_variant	8/8	1		P1	O95125-1
ZNF202	ENST00000529691.1 linkuse as main transcript	c.1678G>A	p.Ala560Thr	missense_variant	7/7	2		P1	O95125-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251402

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000761

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

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:

0.000730

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000330

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

Oct 26, 2022

The c.1678G>A (p.A560T) alteration is located in exon 9 (coding exon 6) of the ZNF202 gene. This alteration results from a G to A substitution at nucleotide position 1678, causing the alanine (A) at amino acid position 560 to be replaced by a threonine (T). 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

0.083

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.4

DANN

Benign

0.84

DEOGEN2

Benign

0.074

T;T;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.60

M_CAP

Benign

0.0037

MetaRNN

Benign

0.021

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.97

N;N;N

MutationTaster

Benign

0.89

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

2.3

N;N;N

REVEL

Benign

0.090

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.13

B;B;B

Vest4

0.068

MutPred

0.49

Gain of phosphorylation at A560 (P = 0.0681);Gain of phosphorylation at A560 (P = 0.0681);Gain of phosphorylation at A560 (P = 0.0681);

MVP

0.29

MPC

0.19

ClinPred

0.036

GERP RS

3.6

Varity_R

0.025

gMVP

0.078

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