19-57327824-C-G

Variant summary

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

The NM_213598.4(ZNF543):​c.362C>G​(p.Ser121Cys) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF543
NM_213598.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.843
Variant links:
Genes affected
ZNF543 (HGNC:25281): (zinc finger protein 543) 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]

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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=0.079129875).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF543NM_213598.4 linkc.362C>G p.Ser121Cys missense_variant Exon 4 of 4 ENST00000321545.5 NP_998763.2 Q08ER8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF543ENST00000321545.5 linkc.362C>G p.Ser121Cys missense_variant Exon 4 of 4 1 NM_213598.4 ENSP00000322545.3 Q08ER8

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
84
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 11, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.362C>G (p.S121C) alteration is located in exon 4 (coding exon 4) of the ZNF543 gene. This alteration results from a C to G substitution at nucleotide position 362, causing the serine (S) at amino acid position 121 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
0.059
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
11
DANN
Benign
0.90
DEOGEN2
Benign
0.0062
T
Eigen
Benign
-0.98
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.092
N
LIST_S2
Benign
0.35
T
M_CAP
Benign
0.0037
T
MetaRNN
Benign
0.079
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.0050
Sift
Uncertain
0.028
D
Sift4G
Benign
0.068
T
Polyphen
0.34
B
Vest4
0.079
MutPred
0.28
Gain of methylation at K122 (P = 0.0178);
MVP
0.29
MPC
0.055
ClinPred
0.12
T
GERP RS
0.49
Varity_R
0.067
gMVP
0.046

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: chr19-57839192; API