rs387907104
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Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_014797.3(ZBTB24):c.958C>T(p.Arg320Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000744 in 1,613,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
ZBTB24
NM_014797.3 stop_gained
NM_014797.3 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 6.21
Genes affected
ZBTB24 (HGNC:21143): (zinc finger and BTB domain containing 24) Predicted to enable DNA-binding transcription factor activity 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 act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in nucleus. Implicated in immunodeficiency-centromeric instability-facial anomalies syndrome 2. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-109476925-G-A is Pathogenic according to our data. Variant chr6-109476925-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 31093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-109476925-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZBTB24 | NM_014797.3 | c.958C>T | p.Arg320Ter | stop_gained | 3/7 | ENST00000230122.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZBTB24 | ENST00000230122.4 | c.958C>T | p.Arg320Ter | stop_gained | 3/7 | 1 | NM_014797.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152128Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250834Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135598
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461536Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727052
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152128Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74310
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Immunodeficiency-centromeric instability-facial anomalies syndrome 2 Pathogenic:3
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 10, 2011 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn | - | PVS1, PM2, PP5 - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 10, 2023 | This sequence change creates a premature translational stop signal (p.Arg320*) in the ZBTB24 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ZBTB24 are known to be pathogenic (PMID: 21596365). This variant is present in population databases (rs387907104, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with clinical features of ZBTB24-related conditions (PMID: 21596365, 30353301). ClinVar contains an entry for this variant (Variation ID: 31093). For these reasons, this variant has been classified as Pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | ZBTB24: PVS1, PM2, PM3 - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A
Vest4
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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