rs74315365
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 9P and 4B. PVS1PP5BS2
The NM_021133.4(RNASEL):c.3G>A(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.0000235 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
RNASEL
NM_021133.4 start_lost
NM_021133.4 start_lost
Scores
2
7
7
Clinical Significance
Conservation
PhyloP100: 4.01
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 5 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PP5
?
Variant 1-182586804-C-T is Pathogenic according to our data. Variant chr1-182586804-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 13005.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
?
High AC in GnomAd at 28 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNASEL | NM_021133.4 | c.3G>A | p.Met1? | start_lost | 2/7 | ENST00000367559.7 | |
RNASEL | XM_047427096.1 | c.3G>A | p.Met1? | start_lost | 2/7 | ||
RNASEL | XM_047427106.1 | c.3G>A | p.Met1? | start_lost | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNASEL | ENST00000367559.7 | c.3G>A | p.Met1? | start_lost | 2/7 | 1 | NM_021133.4 | P1 | |
RNASEL | ENST00000539397.1 | c.3G>A | p.Met1? | start_lost | 2/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152240Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249632Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135244
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461786Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 4AN XY: 727192
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GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74368
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Prostate cancer, hereditary, 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2002 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
A;A;A
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
B;.
Vest4
MutPred
Gain of stability (P = 0.0523);Gain of stability (P = 0.0523);
MVP
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