rs745485838
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_031844.3(HNRNPU):āc.1156A>Gā(p.Ile386Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000379 in 1,582,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 33)
Exomes š: 0.000038 ( 0 hom. )
Consequence
HNRNPU
NM_031844.3 missense
NM_031844.3 missense
Scores
4
13
Clinical Significance
Conservation
PhyloP100: 5.95
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, HNRNPU
BP4
?
Computational evidence support a benign effect (MetaRNN=0.31010887).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNRNPU | NM_031844.3 | c.1156A>G | p.Ile386Val | missense_variant | 6/14 | ENST00000640218.2 | |
HNRNPU | NM_004501.3 | c.1099A>G | p.Ile367Val | missense_variant | 6/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNRNPU | ENST00000640218.2 | c.1156A>G | p.Ile386Val | missense_variant | 6/14 | 1 | NM_031844.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152238Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249678Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134890
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GnomAD4 exome AF: 0.0000377 AC: 54AN: 1430544Hom.: 0 Cov.: 25 AF XY: 0.0000378 AC XY: 27AN XY: 713512
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74380
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 54 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 04, 2023 | This variant has not been reported in the literature in individuals affected with HNRNPU-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt HNRNPU protein function. ClinVar contains an entry for this variant (Variation ID: 446392). This variant is present in population databases (rs745485838, gnomAD 0.005%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 386 of the HNRNPU protein (p.Ile386Val). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;.;.;.;.;.;.
REVEL
Benign
Sift
Benign
T;.;T;.;.;.;.;.;.
Sift4G
Benign
T;.;.;.;.;.;.;.;.
Polyphen
B;B;.;.;.;.;.;.;.
Vest4
MutPred
0.76
.;Gain of ubiquitination at K384 (P = 0.0641);.;.;.;.;.;.;.;
MVP
MPC
0.52
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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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