rs202115297
Positions:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 3P and 14B. PM2PP2BP4_ModerateBP6_Very_StrongBS1
The NM_031844.3(HNRNPU):āc.1952A>Cā(p.Glu651Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,613,582 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 Benign (ā ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 32)
Exomes š: 0.000023 ( 0 hom. )
Consequence
HNRNPU
NM_031844.3 missense
NM_031844.3 missense
Scores
8
9
Clinical Significance
Conservation
PhyloP100: 5.03
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 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=0.11100778).
BP6
?
Variant 1-244856119-T-G is Benign according to our data. Variant chr1-244856119-T-G is described in ClinVar as [Benign]. Clinvar id is 532556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000394 (6/152202) while in subpopulation AMR AF= 0.000393 (6/15282). AF 95% confidence interval is 0.00017. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 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.1952A>C | p.Glu651Ala | missense_variant | 11/14 | ENST00000640218.2 | |
HNRNPU | NM_004501.3 | c.1895A>C | p.Glu632Ala | missense_variant | 11/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HNRNPU | ENST00000640218.2 | c.1952A>C | p.Glu651Ala | missense_variant | 11/14 | 1 | NM_031844.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152202Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
6
AN:
152202
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000119 AC: 30AN: 251096Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135748
GnomAD3 exomes
AF:
AC:
30
AN:
251096
Hom.:
AF XY:
AC XY:
9
AN XY:
135748
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461380Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727034
GnomAD4 exome
AF:
AC:
34
AN:
1461380
Hom.:
Cov.:
31
AF XY:
AC XY:
11
AN XY:
727034
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74348
GnomAD4 genome
?
AF:
AC:
6
AN:
152202
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74348
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
?
AF:
AC:
9
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 54 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2018 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;.;.;.;.;.
REVEL
Benign
Sift
Uncertain
D;.;.;.;.;.;.;.
Sift4G
Benign
T;.;.;.;.;.;.;.
Polyphen
P;P;.;.;.;.;.;.
Vest4
MVP
MPC
0.85
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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