chr3-114339362-C-G
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM1PM2PP5_Moderate
The NM_001348800.3(ZBTB20):c.1869G>C(p.Lys623Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
ZBTB20
NM_001348800.3 missense
NM_001348800.3 missense
Scores
3
8
8
Clinical Significance
Conservation
PhyloP100: 4.81
Publications
2 publications found
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]
ZBTB20 Gene-Disease associations (from GenCC):
- Primrose syndromeInheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
- diabetes mellitusInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
PM1
In a hotspot region, there are 12 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_001348800.3
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-114339362-C-G is Pathogenic according to our data. Variant chr3-114339362-C-G is described in ClinVar as Pathogenic. ClinVar VariationId is 520946.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ZBTB20 | NM_001348800.3 | c.1869G>C | p.Lys623Asn | missense_variant | Exon 12 of 12 | ENST00000675478.1 | NP_001335729.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Mar 09, 2016
Ambry Genetics
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Uncertain
.;.;.;.;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D;.;.;D;.
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;.;.;L;.
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;D;D;D
REVEL
Benign
Sift
Benign
D;D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D
Polyphen
0.57
.;.;.;.;.;P;.
Vest4
MutPred
0.63
.;.;.;.;.;Loss of methylation at K623 (P = 0.0475);.;
MVP
MPC
2.5
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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