16-71448296-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001381984.1(ZNF23):c.1858C>T(p.Arg620Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
ZNF23
NM_001381984.1 missense
NM_001381984.1 missense
Scores
2
3
9
Clinical Significance
Conservation
PhyloP100: -0.168
Genes affected
ZNF23 (HGNC:13023): (zinc finger protein 23) Enables sequence-specific double-stranded 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=0.22823572).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF23 | NM_001381984.1 | c.1858C>T | p.Arg620Trp | missense_variant | 5/5 | ENST00000647773.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF23 | ENST00000647773.2 | c.1858C>T | p.Arg620Trp | missense_variant | 5/5 | NM_001381984.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152004Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000159 AC: 40AN: 251326Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135828
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GnomAD4 exome AF: 0.000143 AC: 209AN: 1461862Hom.: 0 Cov.: 31 AF XY: 0.000147 AC XY: 107AN XY: 727234
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GnomAD4 genome AF: 0.000171 AC: 26AN: 152004Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10AN XY: 74244
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2022 | The c.1729C>T (p.R577W) alteration is located in exon 6 (coding exon 3) of the ZNF23 gene. This alteration results from a C to T substitution at nucleotide position 1729, causing the arginine (R) at amino acid position 577 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;.;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N;N
PrimateAI
Pathogenic
D
Sift4G
Uncertain
D;.;D;D;D
Polyphen
1.0
.;.;D;D;D
Vest4
MVP
MPC
0.45
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at