chr3-114339141-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_001348800.3(ZBTB20):c.2090C>T(p.Pro697Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000539 in 1,613,384 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000054 ( 1 hom. )
Consequence
ZBTB20
NM_001348800.3 missense
NM_001348800.3 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: 3.73
Genes affected
ZBTB20 (HGNC:13503): (zinc finger and BTB domain containing 20) This gene, which was initially designated as dendritic cell-derived BTB/POZ zinc finger (DPZF), belongs to a family of transcription factors with an N-terminal BTB/POZ domain and a C-terminal DNA-bindng zinc finger domain. The BTB/POZ domain is a hydrophobic region of approximately 120 aa which mediates association with other BTB/POZ domain-containing proteins. This gene acts as a transcriptional repressor and plays a role in many processes including neurogenesis, glucose homeostasis, and postnatal growth. Mutations in this gene have been associated with Primrose syndrome as well as the 3q13.31 microdeletion syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, ZBTB20
BP4
?
Computational evidence support a benign effect (MetaRNN=0.12604514).
BP6
?
Variant 3-114339141-G-A is Benign according to our data. Variant chr3-114339141-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2438640.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZBTB20 | NM_001348800.3 | c.2090C>T | p.Pro697Leu | missense_variant | 12/12 | ENST00000675478.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZBTB20 | ENST00000675478.1 | c.2090C>T | p.Pro697Leu | missense_variant | 12/12 | NM_001348800.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000525 AC: 8AN: 152254Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000679 AC: 17AN: 250468Hom.: 0 AF XY: 0.0000813 AC XY: 11AN XY: 135364
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GnomAD4 exome AF: 0.0000541 AC: 79AN: 1461130Hom.: 1 Cov.: 31 AF XY: 0.0000633 AC XY: 46AN XY: 726768
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Primrose syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 27, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 697 of the ZBTB20 protein (p.Pro697Leu). This variant is present in population databases (rs754853149, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ZBTB20-related conditions. ClinVar contains an entry for this variant (Variation ID: 2438640). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ZBTB20 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
0.0030
.;.;.;.;.;B;.
Vest4
MutPred
0.34
.;.;.;.;.;Loss of catalytic residue at P696 (P = 0.0144);.;
MVP
MPC
1.2
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