19-2917095-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173480.3(ZNF57):​c.474C>A​(p.His158Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

ZNF57
NM_173480.3 missense

Scores

4
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.22
Variant links:
Genes affected
ZNF57 (HGNC:13125): (zinc finger protein 57) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF57NM_173480.3 linkc.474C>A p.His158Gln missense_variant Exon 4 of 4 ENST00000306908.10 NP_775751.1 Q68EA5A5HJR3
ZNF57NM_001319083.2 linkc.378C>A p.His126Gln missense_variant Exon 4 of 4 NP_001306012.1 Q68EA5G3V131A5HJR3B4DXX0
ZNF57XM_011527682.3 linkc.378C>A p.His126Gln missense_variant Exon 4 of 4 XP_011525984.1 G3V131

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF57ENST00000306908.10 linkc.474C>A p.His158Gln missense_variant Exon 4 of 4 1 NM_173480.3 ENSP00000303696.5 Q68EA5

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152172
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000796
AC:
20
AN:
251356
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135856
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000289
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:
0.0000792
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000132
AC:
193
AN:
1461798
Hom.:
0
Cov.:
30
AF XY:
0.000133
AC XY:
97
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000158
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152290
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000113
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 17, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.474C>A (p.H158Q) alteration is located in exon 4 (coding exon 4) of the ZNF57 gene. This alteration results from a C to A substitution at nucleotide position 474, causing the histidine (H) at amino acid position 158 to be replaced by a glutamine (Q). 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
Pathogenic
0.67
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.11
CADD
Benign
0.83
DANN
Benign
0.86
DEOGEN2
Benign
0.082
.;T;T;T;T
Eigen
Benign
-0.74
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0063
N
LIST_S2
Benign
0.58
T;T;D;T;T
M_CAP
Benign
0.032
D
MetaRNN
Uncertain
0.53
D;D;D;D;D
MetaSVM
Pathogenic
1.4
D
MutationAssessor
Pathogenic
4.2
.;H;.;.;.
PrimateAI
Benign
0.35
T
PROVEAN
Pathogenic
-6.1
.;D;D;D;.
REVEL
Uncertain
0.38
Sift
Uncertain
0.013
.;D;T;D;.
Sift4G
Uncertain
0.026
D;D;T;D;T
Polyphen
0.96
.;D;.;.;.
Vest4
0.21
MutPred
0.68
.;Gain of MoRF binding (P = 0.0911);.;.;.;
MVP
0.88
MPC
0.040
ClinPred
0.27
T
GERP RS
-3.8
Varity_R
0.17
gMVP
0.049

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: rs190426178; hg19: chr19-2917093; API