Variant 3-48268338-C-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.647C>G(p.Thr216Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,613,900 control chromosomes in the GnomAD database, including 75,546 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 0.29 ( 6841 hom., cov: 32)

Exomes 𝑓: 0.30 ( 68705 hom. )

Consequence

ZNF589
NM_016089.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.451

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=0.0043014884).

BP6

Variant 3-48268338-C-G is Benign according to our data. Variant chr3-48268338-C-G is described in ClinVar as [Benign]. Clinvar id is 3059949.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 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.647C>G	p.Thr216Arg	missense_variant	4/4	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.647C>G	p.Thr216Arg	missense_variant	4/4	1	NM_016089.3	ENSP00000346729.3		Q86UQ0-1

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44093

AN:

151924

Hom.:

6844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.284

GnomAD3 exomes

AF:

0.264

AC:

65999

AN:

250112

Hom.:

9628

AF XY:

0.271

AC XY:

36765

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.155

Gnomad ASJ exome

AF:

0.389

Gnomad EAS exome

AF:

0.120

Gnomad SAS exome

AF:

0.307

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.300

Gnomad OTH exome

AF:

0.285

GnomAD4 exome

AF:

0.301

AC:

440359

AN:

1461858

Hom.:

68705

Cov.:

AF XY:

0.302

AC XY:

219849

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.330

Gnomad4 AMR exome

AF:

0.164

Gnomad4 ASJ exome

AF:

0.390

Gnomad4 EAS exome

AF:

0.119

Gnomad4 SAS exome

AF:

0.311

Gnomad4 FIN exome

AF:

0.203

Gnomad4 NFE exome

AF:

0.314

Gnomad4 OTH exome

AF:

0.309

GnomAD4 genome

AF:

0.290

AC:

44109

AN:

152042

Hom.:

6841

Cov.:

AF XY:

0.284

AC XY:

21129

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.333

Gnomad4 AMR

AF:

0.244

Gnomad4 ASJ

AF:

0.390

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.293

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.298

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.286

Hom.:

5024

Bravo

AF:

0.297

TwinsUK

AF:

0.313

AC:

1161

ALSPAC

AF:

0.312

AC:

1201

ESP6500AA

AF:

0.317

AC:

1304

ESP6500EA

AF:

0.311

AC:

2615

ExAC

AF:

0.268

AC:

32441

Asia WGS

AF:

0.217

AC:

754

AN:

3478

EpiCase

AF:

0.317

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

0.28

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.59

DANN

Benign

0.79

DEOGEN2

Benign

0.0053

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.011

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.55

PrimateAI

Benign

0.29

PROVEAN

Benign

0.54

REVEL

Benign

0.066

Sift

Benign

0.77

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.031

MPC

0.16

ClinPred

0.0015

GERP RS

-2.7

Varity_R

0.048

gMVP

0.057

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