19-57859061-C-T

Variant summary

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

The NM_032828.4(ZNF587):​c.649C>T​(p.Arg217Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. R217H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 27)
Exomes 𝑓: 0.000098 ( 1 hom. )
Failed GnomAD Quality Control

Consequence

ZNF587
NM_032828.4 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.81
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 -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.015454292).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF587NM_032828.4 linkc.649C>T p.Arg217Cys missense_variant Exon 3 of 3 ENST00000339656.8 NP_116217.1 Q96SQ5-1
ZNF587NM_001204817.2 linkc.646C>T p.Arg216Cys 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.649C>T p.Arg217Cys missense_variant Exon 3 of 3 1 NM_032828.4 ENSP00000345479.4 Q96SQ5-1
ENSG00000268750ENST00000593873.6 linkc.*291C>T downstream_gene_variant 4 ENSP00000469133.2 M0QXF5

Frequencies

GnomAD3 genomes
AF:
0.000127
AC:
19
AN:
150084
Hom.:
0
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.0000746
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000332
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000788
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000738
Gnomad OTH
AF:
0.000972
GnomAD3 exomes
AF:
0.000180
AC:
45
AN:
249884
Hom.:
0
AF XY:
0.000192
AC XY:
26
AN XY:
135316
show subpopulations
Gnomad AFR exome
AF:
0.000126
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00103
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.0000887
Gnomad OTH exome
AF:
0.000329
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000978
AC:
143
AN:
1461492
Hom.:
1
Cov.:
32
AF XY:
0.0000977
AC XY:
71
AN XY:
727060
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000504
Gnomad4 SAS exome
AF:
0.000267
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.0000765
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000127
AC:
19
AN:
150084
Hom.:
0
Cov.:
27
AF XY:
0.0000957
AC XY:
7
AN XY:
73170
show subpopulations
Gnomad4 AFR
AF:
0.0000746
Gnomad4 AMR
AF:
0.000332
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000788
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000738
Gnomad4 OTH
AF:
0.000972
Alfa
AF:
0.000169
Hom.:
0
ExAC
AF:
0.000214
AC:
26

ClinVar

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

Submissions by phenotype

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

The c.649C>T (p.R217C) 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 649, causing the arginine (R) at amino acid position 217 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
0.079
BayesDel_addAF
Benign
-0.64
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
0.21
DANN
Benign
0.20
DEOGEN2
Benign
0.0021
T;.;.
Eigen
Benign
-2.1
Eigen_PC
Benign
-2.1
FATHMM_MKL
Benign
0.00097
N
LIST_S2
Benign
0.20
T;T;T
M_CAP
Benign
0.0028
T
MetaRNN
Benign
0.015
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-3.7
N;.;.
PrimateAI
Benign
0.20
T
PROVEAN
Benign
5.6
N;N;N
REVEL
Benign
0.019
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
B;.;.
Vest4
0.056
MutPred
0.49
Loss of MoRF binding (P = 0.0089);.;.;
MVP
0.16
MPC
1.9
ClinPred
0.011
T
GERP RS
-2.4
Varity_R
0.026
gMVP
0.0094

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: rs770671565; hg19: chr19-58370429; COSMIC: COSV57150442; COSMIC: COSV57150442; API