16-2262332-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_080594.4(RNPS1):c.622G>A(p.Val208Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000372 in 1,613,946 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 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
RNPS1
NM_080594.4 missense
NM_080594.4 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 4.43
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 -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2979566).
BS2
?
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNPS1 | NM_080594.4 | c.622G>A | p.Val208Ile | missense_variant | 6/8 | ENST00000320225.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNPS1 | ENST00000320225.10 | c.622G>A | p.Val208Ile | missense_variant | 6/8 | 1 | NM_080594.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251484Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135916
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461736Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25AN XY: 727148
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74368
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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 | Oct 21, 2021 | The c.622G>A (p.V208I) alteration is located in exon 6 (coding exon 5) of the RNPS1 gene. This alteration results from a G to A substitution at nucleotide position 622, causing the valine (V) at amino acid position 208 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T;T;T;T;.;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.;N;.;N;.;N;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
T;T;.;T;T;T;T;T;T;.;.;.
Polyphen
P;P;D;.;P;.;P;.;P;.;.;.
Vest4
MVP
MPC
1.1
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