Variant 19-21423291-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000392288.7(ZNF493):c.632G>A(p.Arg211Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000495 in 1,613,730 control chromosomes in the GnomAD database, including 2 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 0.00054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 2 hom. )

Consequence

ZNF493
ENST00000392288.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.442

Variant links:

Genes affected

ZNF493 (HGNC:23708): (zinc finger protein 493) Predicted to enable DNA-binding transcription activator 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF493 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=0.018570185).

BP6

Variant 19-21423291-G-A is Benign according to our data. Variant chr19-21423291-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2649622.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF493	NM_001076678.3 linkuse as main transcript	c.632G>A	p.Arg211Gln	missense_variant	4/4	ENST00000392288.7	NP_001070146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF493	ENST00000392288.7 linkuse as main transcript	c.632G>A	p.Arg211Gln	missense_variant	4/4	1	NM_001076678.3	ENSP00000376110	P1	Q6ZR52-2
ZNF493	ENST00000355504.4 linkuse as main transcript	c.248G>A	p.Arg83Gln	missense_variant	2/2	1		ENSP00000347691		Q6ZR52-1

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000493

AC:

123

AN:

249664

Hom.:

AF XY:

0.000466

AC XY:

AN XY:

135284

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.000741

Gnomad NFE exome

AF:

0.000789

Gnomad OTH exome

AF:

0.000826

GnomAD4 exome

AF:

0.000490

AC:

716

AN:

1461488

Hom.:

Cov.:

AF XY:

0.000490

AC XY:

356

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.00110

Gnomad4 NFE exome

AF:

0.000527

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000539

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00101

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00115

Hom.:

Bravo

AF:

0.000404

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000815

AC:

ExAC

AF:

0.000560

AC:

EpiCase

AF:

0.000764

EpiControl

AF:

0.000830

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

Aug 01, 2023

ZNF493: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.0

DANN

Benign

0.74

DEOGEN2

Benign

0.0073

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.092

T;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.66

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.63

N;N

REVEL

Benign

0.015

Sift

Benign

0.077

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.093

B;B

Vest4

0.028

MVP

0.17

MPC

0.012

ClinPred

0.0053

GERP RS

-0.46

Varity_R

0.034

gMVP

0.0048

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