chr1-244862498-ATCT-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_031844.3(HNRNPU):βc.837_839delβ(p.Glu279del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: not found (cov: 32)
Exomes π: 0.0000041 ( 0 hom. )
Consequence
HNRNPU
NM_031844.3 inframe_deletion
NM_031844.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.00
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_031844.3. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNRNPU | NM_031844.3 | c.837_839del | p.Glu279del | inframe_deletion | 3/14 | ENST00000640218.2 | |
HNRNPU | NM_004501.3 | c.780_782del | p.Glu260del | inframe_deletion | 3/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNRNPU | ENST00000640218.2 | c.837_839del | p.Glu279del | inframe_deletion | 3/14 | 1 | NM_031844.3 | P3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251462Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135910
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461742Hom.: 0 AF XY: 0.00000688 AC XY: 5AN XY: 727188
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 54 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory of Medical Genetics, University of Torino | Dec 23, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | This variant has been observed in individual(s) with clinical features of epileptic encephalopathy with cerebellar atrophy (PMID: 32319732). 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 372843). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant, c.837_839del, results in the deletion of 1 amino acid(s) of the HNRNPU protein (p.Glu279del), but otherwise preserves the integrity of the reading frame. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 09, 2018 | The c.837_839delAGA variant in the HNRNPU gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.837_839delAGA variant causes an inframe deletion of one codon, Glutamic acid 279, denoted p.Glu279del. Although not observed as homozygous, the c.837_839delAGA variant is observed in 1/17248 (0.006%) alleles from individuals of East Asian background and 2/246250 (0.0008%) total alleles in large population cohorts (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret c.837_839delAGA as a variant of uncertain significance. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at