Variant 3-48241205-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_016089.3(ZNF589):c.34A>G(p.Thr12Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,612,396 control chromosomes in the GnomAD database, including 74,108 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.27 ( 6114 hom., cov: 33)

Exomes 𝑓: 0.30 ( 67994 hom. )

Consequence

ZNF589
NM_016089.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.465

Variant links:

Genes affected

ZNF589 (HGNC:16747): (zinc finger protein 589) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF589 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040002465).

BP6

Variant 3-48241205-A-G is Benign according to our data. Variant chr3-48241205-A-G is described in ClinVar as [Benign]. Clinvar id is 3059438.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF589	NM_016089.3 linkuse as main transcript	c.34A>G	p.Thr12Ala	missense_variant	1/4	ENST00000354698.8	NP_057173.2	Q86UQ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF589	ENST00000354698.8 linkuse as main transcript	c.34A>G	p.Thr12Ala	missense_variant	1/4	1	NM_016089.3	ENSP00000346729.3		Q86UQ0-1

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41812

AN:

152144

Hom.:

6113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.281

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.270

GnomAD3 exomes

AF:

0.258

AC:

62608

AN:

242308

Hom.:

8934

AF XY:

0.267

AC XY:

35277

AN XY:

132216

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.389

Gnomad EAS exome

AF:

0.119

Gnomad SAS exome

AF:

0.305

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.299

Gnomad OTH exome

AF:

0.281

GnomAD4 exome

AF:

0.300

AC:

437774

AN:

1460134

Hom.:

67994

Cov.:

AF XY:

0.301

AC XY:

218705

AN XY:

726426

show subpopulations

Gnomad4 AFR exome

AF:

0.281

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.391

Gnomad4 EAS exome

AF:

0.119

Gnomad4 SAS exome

AF:

0.310

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.314

Gnomad4 OTH exome

AF:

0.306

GnomAD4 genome

AF:

0.275

AC:

41830

AN:

152262

Hom.:

6114

Cov.:

AF XY:

0.271

AC XY:

20152

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.281

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.392

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.292

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.298

Gnomad4 OTH

AF:

0.270

Alfa

AF:

0.298

Hom.:

10918

Bravo

AF:

0.279

TwinsUK

AF:

0.313

AC:

1159

ALSPAC

AF:

0.311

AC:

1197

ESP6500AA

AF:

0.269

AC:

1069

ESP6500EA

AF:

0.308

AC:

2570

ExAC

AF:

0.262

AC:

31590

Asia WGS

AF:

0.213

AC:

739

AN:

3478

EpiCase

AF:

0.318

EpiControl

AF:

0.313

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZNF589-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.7

DANN

Benign

0.46

DEOGEN2

Benign

0.0090

T;T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0065

LIST_S2

Benign

0.24

.;T;T;T

MetaRNN

Benign

0.0040

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

N;.;.;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.11

N;N;N;N

REVEL

Benign

0.010

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.065

T;T;T;T

Polyphen

0.0

B;.;.;B

Vest4

0.025

MPC

0.14

ClinPred

0.00043

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

gMVP

0.10

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