Variant rs2921563 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001353803.2(ZNF875):c.1286G>A(p.Arg429His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 1,613,674 control chromosomes in the GnomAD database, including 2,480 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.080 ( 736 hom., cov: 33)

Exomes 𝑓: 0.042 ( 1744 hom. )

Consequence

ZNF875
NM_001353803.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.333

Variant links:

Genes affected

ZNF875 (HGNC:4928): (zinc finger protein 875) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF875 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014192164).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF875	NM_001353803.2 linkuse as main transcript	c.1286G>A	p.Arg429His	missense_variant	5/5	ENST00000392153.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF875	ENST00000392153.8 linkuse as main transcript	c.1286G>A	p.Arg429His	missense_variant	5/5	1	NM_001353803.2	P4	P10072-2

Frequencies

GnomAD3 genomes

AF:

0.0801

AC:

12151

AN:

151692

Hom.:

735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0850

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.0827

Gnomad SAS

AF:

0.0212

Gnomad FIN

AF:

0.0618

Gnomad MID

AF:

0.0224

Gnomad NFE

AF:

0.0342

Gnomad OTH

AF:

0.0697

GnomAD3 exomes

AF:

0.0539

AC:

13547

AN:

251320

Hom.:

560

AF XY:

0.0487

AC XY:

6620

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.0739

Gnomad ASJ exome

AF:

0.0375

Gnomad EAS exome

AF:

0.0884

Gnomad SAS exome

AF:

0.0221

Gnomad FIN exome

AF:

0.0593

Gnomad NFE exome

AF:

0.0341

Gnomad OTH exome

AF:

0.0516

GnomAD4 exome

AF:

0.0417

AC:

60891

AN:

1461864

Hom.:

1744

Cov.:

AF XY:

0.0407

AC XY:

29614

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.173

Gnomad4 AMR exome

AF:

0.0764

Gnomad4 ASJ exome

AF:

0.0368

Gnomad4 EAS exome

AF:

0.0822

Gnomad4 SAS exome

AF:

0.0225

Gnomad4 FIN exome

AF:

0.0610

Gnomad4 NFE exome

AF:

0.0350

Gnomad4 OTH exome

AF:

0.0532

GnomAD4 genome

AF:

0.0801

AC:

12157

AN:

151810

Hom.:

736

Cov.:

AF XY:

0.0795

AC XY:

5901

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.172

Gnomad4 AMR

AF:

0.0853

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.0825

Gnomad4 SAS

AF:

0.0206

Gnomad4 FIN

AF:

0.0618

Gnomad4 NFE

AF:

0.0342

Gnomad4 OTH

AF:

0.0699

Alfa

AF:

0.0416

Hom.:

432

Bravo

AF:

0.0873

TwinsUK

AF:

0.0307

AC:

114

ALSPAC

AF:

0.0348

AC:

134

ESP6500AA

AF:

0.165

AC:

725

ESP6500EA

AF:

0.0337

AC:

290

ExAC

AF:

0.0539

AC:

6539

Asia WGS

AF:

0.0690

AC:

239

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

0.052

Eigen_PC

Benign

-0.068

FATHMM_MKL

Benign

0.026

MetaRNN

Benign

0.0014

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.97

P;P;P;P;P;P;P

PrimateAI

Benign

0.32

Sift4G

Uncertain

0.038

D;D;T;T;T;T

Polyphen

0.99, 1.0, 1.0

.;.;D;.;D;D

Vest4

0.16

MPC

0.094

ClinPred

0.040

GERP RS

0.79

Varity_R

0.086

gMVP

0.072

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over