Genetic Variant ZNF587:p.Arg173Cys (chr19-57858929-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_032828.4(ZNF587):c.517C>T(p.Arg173Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 26)

Exomes 𝑓: 0.00011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF587
NM_032828.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.71

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:

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:

ENSG00000268750 (HGNC:):

ENSG00000268750 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02768138).

BP6

Variant 19-57858929-C-T is Benign according to our data. Variant chr19-57858929-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2354711.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF587	NM_032828.4 link	c.517C>T	p.Arg173Cys	missense_variant	Exon 3 of 3	ENST00000339656.8	NP_116217.1	Q96SQ5-1
ZNF587	NM_001204817.2 link	c.514C>T	p.Arg172Cys	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.517C>T	p.Arg173Cys	missense_variant	Exon 3 of 3	1	NM_032828.4	ENSP00000345479.4		Q96SQ5-1
ENSG00000268750	ENST00000593873.6 link	c.*159C>T		downstream_gene_variant		4		ENSP00000469133.2		M0QXF5

Frequencies

GnomAD3 genomes

AF:

0.0000531

AC:

AN:

150752

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000494

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000627

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000164

AC:

AN:

250726

Hom.:

AF XY:

0.000229

AC XY:

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000113

AC:

165

AN:

1461308

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

103

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000661

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.0000738

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000530

AC:

AN:

150868

Hom.:

Cov.:

AF XY:

0.0000950

AC XY:

AN XY:

73714

show subpopulations

Gnomad4 AFR

AF:

0.0000492

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000628

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000480

Hom.:

ExAC

AF:

0.000181

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 11, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.38

DANN

Benign

0.67

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0040

M_CAP

Benign

0.0029

MetaRNN

Benign

0.028

Vest4

0.075

MVP

0.17

ClinPred

0.0083

GERP RS

-2.8

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