19-19891794-C-T

Variant summary

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

The NM_021047.3(ZNF253):​c.547C>T​(p.Arg183Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

ZNF253
NM_021047.3 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.02
Variant links:
Genes affected
ZNF253 (HGNC:13497): (zinc finger protein 253) 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, DNA-templated. Predicted to be located 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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06887007).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF253NM_021047.3 linkc.547C>T p.Arg183Trp missense_variant Exon 4 of 4 ENST00000589717.2 NP_066385.2 O75346-1
ZNF253NM_001331133.1 linkc.355C>T p.Arg119Trp missense_variant Exon 3 of 3 NP_001318062.1 O75346
ZNF253NM_001331134.1 linkc.319C>T p.Arg107Trp missense_variant Exon 2 of 2 NP_001318063.1 O75346-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF253ENST00000589717.2 linkc.547C>T p.Arg183Trp missense_variant Exon 4 of 4 1 NM_021047.3 ENSP00000468720.1 O75346-1
ZNF253ENST00000355650.4 linkc.319C>T p.Arg107Trp missense_variant Exon 2 of 2 1 ENSP00000347868.4 O75346-2
ZNF253ENST00000592725.1 linkc.355C>T p.Arg119Trp missense_variant Exon 3 of 3 2 ENSP00000467235.1 K7EP55

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152228
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
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:
0.0000440
AC:
11
AN:
249800
Hom.:
0
AF XY:
0.0000590
AC XY:
8
AN XY:
135522
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000442
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000294
AC:
43
AN:
1461734
Hom.:
0
Cov.:
32
AF XY:
0.0000316
AC XY:
23
AN XY:
727170
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152228
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0000482
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
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000578
AC:
7
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 19, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.547C>T (p.R183W) alteration is located in exon 4 (coding exon 4) of the ZNF253 gene. This alteration results from a C to T substitution at nucleotide position 547, causing the arginine (R) at amino acid position 183 to be replaced by a tryptophan (W). 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
0.18
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
11
DANN
Benign
0.87
DEOGEN2
Benign
0.016
.;T;.;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.000080
N
LIST_S2
Benign
0.040
T;T;T;T
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.069
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.095
.;N;.;.
PrimateAI
Benign
0.35
T
REVEL
Benign
0.019
Sift4G
Benign
0.41
T;T;T;.
Polyphen
0.022
.;B;.;.
Vest4
0.084, 0.083
MutPred
0.34
.;Loss of disorder (P = 0.0103);.;.;
MVP
0.19
MPC
0.11
ClinPred
0.014
T
GERP RS
0.81
Varity_R
0.037
gMVP
0.039

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: rs763411661; hg19: chr19-20002603; API