Variant rs12354886 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_145312.4(ZNF485):c.754G>A(p.Ala252Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,613,688 control chromosomes in the GnomAD database, including 42,162 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.22 ( 4025 hom., cov: 33)

Exomes 𝑓: 0.22 ( 38137 hom. )

Consequence

ZNF485
NM_145312.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.448

Variant links:

Genes affected

ZNF485 (HGNC:23440): (zinc finger protein 485) 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]

ZNF485 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=0.0046267807).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF485	NM_145312.4 linkuse as main transcript	c.754G>A	p.Ala252Thr	missense_variant	5/5	ENST00000361807.8	NP_660355.2	Q8NCK3-1A0A024R7T5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF485	ENST00000361807.8 linkuse as main transcript	c.754G>A	p.Ala252Thr	missense_variant	5/5	1	NM_145312.4	ENSP00000354694.3		Q8NCK3-1
ZNF485	ENST00000374435.3 linkuse as main transcript	c.754G>A	p.Ala252Thr	missense_variant	5/5	1		ENSP00000363558.3		Q8NCK3-1

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34089

AN:

151846

Hom.:

4023

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.00214

Gnomad SAS

AF:

0.186

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.224

GnomAD3 exomes

AF:

0.193

AC:

48508

AN:

251072

Hom.:

5299

AF XY:

0.193

AC XY:

26240

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.270

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.000925

Gnomad SAS exome

AF:

0.188

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.229

Gnomad OTH exome

AF:

0.207

GnomAD4 exome

AF:

0.223

AC:

325407

AN:

1461726

Hom.:

38137

Cov.:

AF XY:

0.222

AC XY:

161147

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.269

Gnomad4 AMR exome

AF:

0.164

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.000655

Gnomad4 SAS exome

AF:

0.186

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.238

Gnomad4 OTH exome

AF:

0.217

GnomAD4 genome

AF:

0.224

AC:

34110

AN:

151962

Hom.:

4025

Cov.:

AF XY:

0.217

AC XY:

16123

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.273

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.00214

Gnomad4 SAS

AF:

0.187

Gnomad4 FIN

AF:

0.150

Gnomad4 NFE

AF:

0.234

Gnomad4 OTH

AF:

0.222

Alfa

AF:

0.224

Hom.:

9789

Bravo

AF:

0.228

TwinsUK

AF:

0.240

AC:

890

ALSPAC

AF:

0.234

AC:

900

ESP6500AA

AF:

0.268

AC:

1183

ESP6500EA

AF:

0.232

AC:

1995

ExAC

AF:

0.196

AC:

23788

Asia WGS

AF:

0.0920

AC:

321

AN:

3478

EpiCase

AF:

0.230

EpiControl

AF:

0.222

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.0044

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00023

LIST_S2

Benign

0.16

.;T

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.95

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

0.29

N;N

REVEL

Benign

0.012

Sift

Benign

0.61

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.0010

B;B

Vest4

0.018

MPC

0.12

ClinPred

0.00018

GERP RS

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.065

gMVP

0.012

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