Variant 19-57778933-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017652.4(ZNF586):c.346C>T(p.Arg116Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

ZNF586
NM_017652.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.392

Variant links:

Genes affected

ZNF586 (HGNC:25949): (zinc finger protein 586) Predicted to enable DNA-binding transcription factor 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]

ZNF586 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09548077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF586	NM_017652.4 linkuse as main transcript	c.346C>T	p.Arg116Cys	missense_variant	3/3	ENST00000396154.7	NP_060122.2	Q9NXT0-1
ZNF586	NM_001204814.2 linkuse as main transcript	c.217C>T	p.Arg73Cys	missense_variant	4/4		NP_001191743.1	Q9NXT0-3
ZNF586	NM_001077426.3 linkuse as main transcript	c.219C>T	p.Phe73Phe	synonymous_variant	2/2		NP_001070894.1	Q9NXT0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF586	ENST00000396154.7 linkuse as main transcript	c.346C>T	p.Arg116Cys	missense_variant	3/3	1	NM_017652.4	ENSP00000379458.1		Q9NXT0-1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000168

AC:

AN:

250132

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.0000645

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000189

AC:

276

AN:

1461868

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

151

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000219

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000237

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000294

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000235

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.346C>T (p.R116C) alteration is located in exon 3 (coding exon 3) of the ZNF586 gene. This alteration results from a C to T substitution at nucleotide position 346, causing the arginine (R) at amino acid position 116 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.028

.;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.095

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.59

.;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.079

Sift

Pathogenic

0.0

D;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.075

MVP

0.055

MPC

0.10

ClinPred

0.065

GERP RS

0.53

Varity_R

0.057

gMVP

0.21

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