16-2264312-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_080594.4(RNPS1):c.91C>T(p.Arg31Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000135 in 1,614,134 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
RNPS1
NM_080594.4 missense
NM_080594.4 missense
Scores
5
2
12
Clinical Significance
Conservation
PhyloP100: 3.74
Genes affected
RNPS1 (HGNC:10080): (RNA binding protein with serine rich domain 1) This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein binds to the mRNA and remains bound after nuclear export, acting as a nucleocytoplasmic shuttling protein. This protein contains many serine residues. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.2184273).
BS2
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNPS1 | NM_080594.4 | c.91C>T | p.Arg31Cys | missense_variant | 3/8 | ENST00000320225.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNPS1 | ENST00000320225.10 | c.91C>T | p.Arg31Cys | missense_variant | 3/8 | 1 | NM_080594.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152132Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251482Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135914
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GnomAD4 exome AF: 0.000143 AC: 209AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.000139 AC XY: 101AN XY: 727242
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152250Hom.: 0 Cov.: 31 AF XY: 0.0000537 AC XY: 4AN XY: 74432
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 04, 2024 | The c.91C>T (p.R31C) alteration is located in exon 3 (coding exon 2) of the RNPS1 gene. This alteration results from a C to T substitution at nucleotide position 91, causing the arginine (R) at amino acid position 31 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;T;.;T;T;T;T;T;T;T;T;.;T;T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D;.;.;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;L;L;L;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;D;D;D;D;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T;T;T;T;T;D;.;T;T;D
Sift4G
Benign
T;T;.;T;T;T;.;.;.;.;T;.;T;T;T;T
Polyphen
D;D;D;D;D;D;.;.;.;.;.;.;.;.;.;.
Vest4
MVP
MPC
0.63
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