19-57858627-C-T

Variant summary

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

The NM_032828.4(ZNF587):​c.215C>T​(p.Ser72Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 27)

Consequence

ZNF587
NM_032828.4 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.148
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]

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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=0.1627503).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF587NM_032828.4 linkc.215C>T p.Ser72Phe missense_variant Exon 3 of 3 ENST00000339656.8 NP_116217.1 Q96SQ5-1
ZNF587NM_001204817.2 linkc.212C>T p.Ser71Phe missense_variant Exon 3 of 3 NP_001191746.1 Q96SQ5-2
LOC124904782XR_007067358.1 linkn.-51G>A upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF587ENST00000339656.8 linkc.215C>T p.Ser72Phe missense_variant Exon 3 of 3 1 NM_032828.4 ENSP00000345479.4 Q96SQ5-1
ENSG00000268750ENST00000593873.6 linkc.85C>T p.Leu29Leu synonymous_variant Exon 2 of 2 4 ENSP00000469133.2 M0QXF5

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
27

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 29, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.215C>T (p.S72F) 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 215, causing the serine (S) at amino acid position 72 to be replaced by a phenylalanine (F). 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
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
10
DANN
Benign
0.83
DEOGEN2
Benign
0.037
.;.;.;T;.;.
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.0085
N
LIST_S2
Benign
0.67
T;T;T;T;T;D
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.16
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
.;.;.;L;.;.
PrimateAI
Benign
0.26
T
PROVEAN
Uncertain
-3.0
.;.;.;D;D;D
REVEL
Benign
0.034
Sift
Uncertain
0.013
.;.;.;D;D;D
Sift4G
Benign
0.26
T;T;T;D;T;D
Polyphen
0.97
.;.;.;D;.;.
Vest4
0.070, 0.11, 0.080
MutPred
0.38
.;.;Loss of disorder (P = 0.0044);Loss of disorder (P = 0.0044);.;.;
MVP
0.36
MPC
0.91
ClinPred
0.33
T
GERP RS
1.4
Varity_R
0.074
gMVP
0.0083

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-58369995; API