1-182581247-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_021133.4(RNASEL):c.1883G>A(p.Ser628Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,106 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Consequence
RNASEL
NM_021133.4 missense
NM_021133.4 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 0.182
Genes affected
RNASEL (HGNC:10050): (ribonuclease L) This gene encodes a component of the interferon-regulated 2-5A system that functions in the antiviral and antiproliferative roles of interferons. The protein is involved in innate immunity and is active against multiple RNA viruses, including the influenza and SARS-CoV-2 viruses. Mutations in this gene have been associated with predisposition to prostate cancer and this gene is a candidate for the hereditary prostate cancer 1 (HPC1) allele. [provided by RefSeq, Nov 2021]
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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;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNASEL | NM_021133.4 | c.1883G>A | p.Ser628Asn | missense_variant | 5/7 | ENST00000367559.7 | |
RNASEL | XM_047427096.1 | c.1883G>A | p.Ser628Asn | missense_variant | 5/7 | ||
RNASEL | XM_047427106.1 | c.1883G>A | p.Ser628Asn | missense_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNASEL | ENST00000367559.7 | c.1883G>A | p.Ser628Asn | missense_variant | 5/7 | 1 | NM_021133.4 | P1 | |
RNASEL | ENST00000539397.1 | c.1883G>A | p.Ser628Asn | missense_variant | 5/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152106Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD4 exome Cov.: 32
GnomAD4 exome
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32
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152106Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74300
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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 | Dec 22, 2023 | The c.1883G>A (p.S628N) alteration is located in exon 5 (coding exon 4) of the RNASEL gene. This alteration results from a G to A substitution at nucleotide position 1883, causing the serine (S) at amino acid position 628 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Loss of phosphorylation at S628 (P = 0.0485);Loss of phosphorylation at S628 (P = 0.0485);
MVP
MPC
ClinPred
T
GERP RS
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