rs778730784
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_031844.3(HNRNPU):c.1434C>T(p.Asn478=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,613,634 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
HNRNPU
NM_031844.3 synonymous
NM_031844.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.16
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 Benign. Variant got -15 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 1-244858071-G-A is Benign according to our data. Variant chr1-244858071-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 446404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.16 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000146 (214/1461730) while in subpopulation NFE AF= 0.000184 (205/1111870). AF 95% confidence interval is 0.000163. There are 0 homozygotes in gnomad4_exome. There are 93 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HNRNPU | NM_031844.3 | c.1434C>T | p.Asn478= | synonymous_variant | 7/14 | ENST00000640218.2 | |
HNRNPU | NM_004501.3 | c.1377C>T | p.Asn459= | synonymous_variant | 7/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNRNPU | ENST00000640218.2 | c.1434C>T | p.Asn478= | synonymous_variant | 7/14 | 1 | NM_031844.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151810Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251404Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135886
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GnomAD4 exome AF: 0.000146 AC: 214AN: 1461730Hom.: 0 Cov.: 32 AF XY: 0.000128 AC XY: 93AN XY: 727182
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GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151904Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74212
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 02, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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