rs201768786

Variant summary

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

The NM_173480.3(ZNF57):​c.650C>G​(p.Thr217Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T217I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

ZNF57
NM_173480.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.26
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]

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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=0.086603165).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF57NM_173480.3 linkc.650C>G p.Thr217Ser missense_variant Exon 4 of 4 ENST00000306908.10 NP_775751.1 Q68EA5A5HJR3
ZNF57NM_001319083.2 linkc.554C>G p.Thr185Ser missense_variant Exon 4 of 4 NP_001306012.1 Q68EA5G3V131A5HJR3B4DXX0
ZNF57XM_011527682.3 linkc.554C>G p.Thr185Ser 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.650C>G p.Thr217Ser missense_variant Exon 4 of 4 1 NM_173480.3 ENSP00000303696.5 Q68EA5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461776
Hom.:
0
Cov.:
79
AF XY:
0.00000413
AC XY:
3
AN XY:
727170
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.036
DANN
Benign
0.87
DEOGEN2
Benign
0.0031
.;T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0031
N
LIST_S2
Benign
0.36
T;T;T
M_CAP
Benign
0.00084
T
MetaRNN
Benign
0.087
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.69
.;N;.
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.4
.;N;N
REVEL
Benign
0.017
Sift
Benign
0.16
.;T;T
Sift4G
Benign
0.14
T;T;T
Polyphen
0.15
.;B;.
Vest4
0.039
MutPred
0.47
.;Loss of glycosylation at T217 (P = 0.0547);.;
MVP
0.22
MPC
0.030
ClinPred
0.080
T
GERP RS
-4.7
Varity_R
0.020
gMVP
0.0093

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: chr19-2917269; API