rs1553283831
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_031844.3(HNRNPU):c.596_597insC(p.Pro200AlafsTer14) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HNRNPU
NM_031844.3 frameshift
NM_031844.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.13
Genes affected
HNRNPU (HGNC:5048): (heterogeneous nuclear ribonucleoprotein U) This gene encodes a member of a family of proteins that bind nucleic acids and function in the formation of ribonucleoprotein complexes in the nucleus with heterogeneous nuclear RNA (hnRNA). The encoded protein has affinity for both RNA and DNA, and binds scaffold-attached region (SAR) DNA. Mutations in this gene have been associated with epileptic encephalopathy, early infantile, 54. A pseudogene of this gene has been identified on chromosome 14. [provided by RefSeq, Jun 2017]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 1-244863711-C-CG is Pathogenic according to our data. Variant chr1-244863711-C-CG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438295.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNRNPU | NM_031844.3 | c.596_597insC | p.Pro200AlafsTer14 | frameshift_variant | 1/14 | ENST00000640218.2 | |
HNRNPU | NM_004501.3 | c.596_597insC | p.Pro200AlafsTer24 | frameshift_variant | 1/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNRNPU | ENST00000640218.2 | c.596_597insC | p.Pro200AlafsTer14 | frameshift_variant | 1/14 | 1 | NM_031844.3 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1414450Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 701916
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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1414450
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34
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0
AN XY:
701916
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Intellectual disability Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals | Apr 08, 2016 | - - |
Computational scores
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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