Variant 19-22663850-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000456783.3(ZNF492):c.181A>C(p.Asn61His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,560,826 control chromosomes in the GnomAD database, including 24 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0031 ( 23 hom. )

Consequence

ZNF492
ENST00000456783.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.154

Variant links:

Genes affected

ZNF492 (HGNC:23707): (zinc finger protein 492) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF492 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005381167).

BP6

Variant 19-22663850-A-C is Benign according to our data. Variant chr19-22663850-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3067208.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF492	NM_020855.3 linkuse as main transcript	c.181A>C	p.Asn61His	missense_variant	4/4	ENST00000456783.3	NP_065906.1	Q9P255
ZNF492	XM_047439130.1 linkuse as main transcript	c.181A>C	p.Asn61His	missense_variant	4/4		XP_047295086.1
ZNF492	XM_047439131.1 linkuse as main transcript	c.85A>C	p.Asn29His	missense_variant	3/3		XP_047295087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF492	ENST00000456783.3 linkuse as main transcript	c.181A>C	p.Asn61His	missense_variant	4/4	1	NM_020855.3	ENSP00000413660.2		Q9P255

Frequencies

GnomAD3 genomes

AF:

0.00226

AC:

343

AN:

151668

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000657

Gnomad AMI

AF:

0.00441

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00349

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00270

AC:

537

AN:

199248

Hom.:

AF XY:

0.00275

AC XY:

297

AN XY:

108174

show subpopulations

Gnomad AFR exome

AF:

0.000976

Gnomad AMR exome

AF:

0.000544

Gnomad ASJ exome

AF:

0.00495

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000905

Gnomad FIN exome

AF:

0.00242

Gnomad NFE exome

AF:

0.00430

Gnomad OTH exome

AF:

0.00463

GnomAD4 exome

AF:

0.00309

AC:

4358

AN:

1409040

Hom.:

Cov.:

AF XY:

0.00300

AC XY:

2093

AN XY:

697602

show subpopulations

Gnomad4 AFR exome

AF:

0.000626

Gnomad4 AMR exome

AF:

0.000766

Gnomad4 ASJ exome

AF:

0.00548

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000650

Gnomad4 FIN exome

AF:

0.00325

Gnomad4 NFE exome

AF:

0.00350

Gnomad4 OTH exome

AF:

0.00326

GnomAD4 genome

AF:

0.00226

AC:

343

AN:

151786

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

157

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.000655

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.00349

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00344

Hom.:

Bravo

AF:

0.00210

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000554

AC:

ESP6500EA

AF:

0.00329

AC:

ExAC

AF:

0.00279

AC:

334

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

ZNF492: PP2, BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.5

DANN

Benign

0.90

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.060

M_CAP

Benign

0.0011

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.94

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.9

REVEL

Benign

0.049

Sift

Uncertain

0.015

Sift4G

Uncertain

0.051

Polyphen

0.71

Vest4

0.097

MVP

0.43

MPC

2.4

ClinPred

0.015

GERP RS

0.035

Varity_R

0.063

gMVP

0.010

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