19-57858893-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032828.4(ZNF587):c.481C>T(p.Arg161Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 149,648 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R161H) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000034 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF587
NM_032828.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0550

Variant links:

Genes affected

ZNF587 (HGNC:30955): (zinc finger protein 587) 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]

ZNF587 links:

ENSG00000268750 (HGNC:):

ENSG00000268750 links:

ZNF814 (HGNC:33258): (zinc finger protein 814) 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]

ZNF814 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01539436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF587	NM_032828.4 link	c.481C>T	p.Arg161Cys	missense_variant	Exon 3 of 3	ENST00000339656.8	NP_116217.1	Q96SQ5-1
ZNF587	NM_001204817.2 link	c.478C>T	p.Arg160Cys	missense_variant	Exon 3 of 3		NP_001191746.1	Q96SQ5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF587	ENST00000339656.8 link	c.481C>T	p.Arg161Cys	missense_variant	Exon 3 of 3	1	NM_032828.4	ENSP00000345479.4		Q96SQ5-1
ENSG00000268750	ENST00000593873.6 link	c.*123C>T		3_prime_UTR_variant	Exon 2 of 2	4		ENSP00000469133.2		M0QXF5

Frequencies

GnomAD3 genomes

AF:

0.000254

AC:

AN:

149552

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000947

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000781

AC:

AN:

243320

Hom.:

AF XY:

0.0000682

AC XY:

AN XY:

131920

show subpopulations

Gnomad AFR exome

AF:

0.000975

Gnomad AMR exome

AF:

0.0000593

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000340

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000342

AC:

AN:

1460912

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

726796

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000254

AC:

AN:

149648

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

AN XY:

72952

show subpopulations

Gnomad4 AFR

AF:

0.000944

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ESP6500AA

AF:

0.00122

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000149

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.481C>T (p.R161C) alteration is located in exon 3 (coding exon 3) of the ZNF587 gene. This alteration results from a C to T substitution at nucleotide position 481, causing the arginine (R) at amino acid position 161 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

0.14

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.8

DANN

Benign

0.050

DEOGEN2

Benign

0.0017

.;.;.;T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.38

.;T;T;T;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.015

T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.89

.;.;.;N;.;.

PrimateAI

Benign

0.18

PROVEAN

Benign

7.7

.;.;.;N;N;N

REVEL

Benign

0.019

Sift

Benign

1.0

.;.;.;T;T;T

Sift4G

Benign

0.22

T;T;T;T;T;T

Polyphen

0.0

.;.;.;B;.;.

Vest4

0.064, 0.091, 0.061

MVP

0.24

MPC

1.2

ClinPred

0.0037

GERP RS

-0.28

Varity_R

0.040

gMVP

0.0055

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