chr10-79208452-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_020338.4(ZMIZ1):c.174+3G>A variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.00000411 in 1,459,932 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: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
ZMIZ1
NM_020338.4 splice_donor_region, intron
NM_020338.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.004067
2
Clinical Significance
Conservation
PhyloP100: 5.82
Genes affected
ZMIZ1 (HGNC:16493): (zinc finger MIZ-type containing 1) This gene encodes a member of the PIAS (protein inhibitor of activated STAT) family of proteins. The encoded protein regulates the activity of various transcription factors, including the androgen receptor, Smad3/4, and p53. The encoded protein may also play a role in sumoylation. A translocation between this locus on chromosome 10 and the protein tyrosine kinase ABL1 locus on chromosome 9 has been associated with acute lymphoblastic leukemia. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZMIZ1 | NM_020338.4 | c.174+3G>A | splice_donor_region_variant, intron_variant | ENST00000334512.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZMIZ1 | ENST00000334512.10 | c.174+3G>A | splice_donor_region_variant, intron_variant | 5 | NM_020338.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248670Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134740
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1459932Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 726372
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GnomAD4 genome ? Cov.: 32
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Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 09, 2023 | This sequence change falls in intron 6 of the ZMIZ1 gene. It does not directly change the encoded amino acid sequence of the ZMIZ1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs769763468, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ZMIZ1-related conditions. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at