19-57858879-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032828.4(ZNF587):c.467C>T(p.Ser156Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000041 ( 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: -0.643

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.090599746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF587	NM_032828.4 link	c.467C>T	p.Ser156Leu	missense_variant	Exon 3 of 3	ENST00000339656.8	NP_116217.1	Q96SQ5-1
ZNF587	NM_001204817.2 link	c.464C>T	p.Ser155Leu	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.467C>T	p.Ser156Leu	missense_variant	Exon 3 of 3	1	NM_032828.4	ENSP00000345479.4		Q96SQ5-1
ENSG00000268750	ENST00000593873.6 link	c.*109C>T		3_prime_UTR_variant	Exon 2 of 2	4		ENSP00000469133.2		M0QXF5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148488

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000200

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:

0.00000411

AC:

AN:

243374

Hom.:

AF XY:

0.00000757

AC XY:

AN XY:

132176

show subpopulations

Gnomad AFR exome

AF:

0.0000660

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

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:

0.00000411

AC:

AN:

1460820

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726746

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000539

AC:

AN:

148488

Hom.:

Cov.:

AF XY:

0.0000554

AC XY:

AN XY:

72234

show subpopulations

Gnomad4 AFR

AF:

0.000200

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.467C>T (p.S156L) 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 467, causing the serine (S) at amino acid position 156 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.2

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

.;.;.;T;.;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.47

.;T;T;T;T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.091

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;.;.;L;.;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.0

.;.;.;N;N;N

REVEL

Benign

0.049

Sift

Benign

0.32

.;.;.;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.78

.;.;.;P;.;.

Vest4

0.10, 0.11, 0.10

MutPred

0.45

.;.;Loss of phosphorylation at S156 (P = 0.0053);Loss of phosphorylation at S156 (P = 0.0053);.;.;

MVP

0.33

MPC

1.1

ClinPred

0.069

GERP RS

2.1

Varity_R

0.018

gMVP

0.0051

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