chr1-30936807-CGTGA-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_001020658.2(PUM1):c.3267_3270del(p.His1090ProfsTer16) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 30)
Consequence
PUM1
NM_001020658.2 frameshift
NM_001020658.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
PUM1 (HGNC:14957): (pumilio RNA binding family member 1) This gene encodes a member of the PUF family, evolutionarily conserved RNA-binding proteins related to the Pumilio proteins of Drosophila and the fem-3 mRNA binding factor proteins of C. elegans. The encoded protein contains a sequence-specific RNA binding domain comprised of eight repeats and N- and C-terminal flanking regions, and serves as a translational regulator of specific mRNAs by binding to their 3' untranslated regions. The evolutionarily conserved function of the encoded protein in invertebrates and lower vertebrates suggests that the human protein may be involved in translational regulation of embryogenesis, and cell development and differentiation. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0841 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PUM1 | NM_001020658.2 | c.3267_3270del | p.His1090ProfsTer16 | frameshift_variant | 21/22 | ENST00000426105.7 | |
PUM1 | NM_014676.3 | c.3261_3264del | p.His1088ProfsTer16 | frameshift_variant | 21/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PUM1 | ENST00000426105.7 | c.3267_3270del | p.His1090ProfsTer16 | frameshift_variant | 21/22 | 1 | NM_001020658.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 genomes
?
Cov.:
30
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 30
GnomAD4 genome
?
Cov.:
30
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Neurodevelopmental disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes | Sep 16, 2020 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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
No publications associated with this variant yet.