19-57858879-C-T

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

1
17

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]
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]

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
ZNF587NM_032828.4 linkc.467C>T p.Ser156Leu missense_variant Exon 3 of 3 ENST00000339656.8 NP_116217.1 Q96SQ5-1
ZNF587NM_001204817.2 linkc.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
ZNF587ENST00000339656.8 linkc.467C>T p.Ser156Leu missense_variant Exon 3 of 3 1 NM_032828.4 ENSP00000345479.4 Q96SQ5-1
ENSG00000268750ENST00000593873.6 linkc.*109C>T 3_prime_UTR_variant Exon 2 of 2 4 ENSP00000469133.2 M0QXF5

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
8
AN:
148488
Hom.:
0
Cov.:
26
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:
1
AN:
243374
Hom.:
0
AF XY:
0.00000757
AC XY:
1
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:
6
AN:
1460820
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
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:
8
AN:
148488
Hom.:
0
Cov.:
26
AF XY:
0.0000554
AC XY:
4
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
T
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
N
LIST_S2
Benign
0.47
.;T;T;T;T;T
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.091
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
.;.;.;L;.;.
PrimateAI
Benign
0.23
T
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
T
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.

Other links and lift over

dbSNP: rs1212538218; hg19: chr19-58370247; API