rs1553270634
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP2PP3PP5_Moderate
The NM_205768.3(ZBTB18):c.1444C>T(p.Arg482Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R482H) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
ZBTB18
NM_205768.3 missense
NM_205768.3 missense
Scores
9
6
4
Clinical Significance
Conservation
PhyloP100: 4.75
Genes affected
ZBTB18 (HGNC:13030): (zinc finger and BTB domain containing 18) This gene encodes a C2H2-type zinc finger protein which acts a transcriptional repressor of genes involved in neuronal development. The encoded protein recognizes a specific sequence motif and recruits components of chromatin to target genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_205768.3
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ZBTB18. . Gene score misZ 3.4305 (greater than the threshold 3.09). Trascript score misZ 4.2468 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 22, complex neurodevelopmental disorder.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.776
PP5
Variant 1-244055218-C-T is Pathogenic according to our data. Variant chr1-244055218-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 548012.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZBTB18 | NM_205768.3 | c.1444C>T | p.Arg482Cys | missense_variant | 2/2 | ENST00000358704.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZBTB18 | ENST00000358704.4 | c.1444C>T | p.Arg482Cys | missense_variant | 2/2 | 1 | NM_205768.3 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual disability, autosomal dominant 22 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Nov 21, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
.;D
REVEL
Uncertain
Sift
Pathogenic
.;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.001);.;
MVP
MPC
2.2
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