11-498922-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_203387.3(RNH1):c.626G>A(p.Cys209Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000409 in 1,612,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000041 ( 0 hom. )
Consequence
RNH1
NM_203387.3 missense
NM_203387.3 missense
Scores
6
9
3
Clinical Significance
Conservation
PhyloP100: 5.98
Genes affected
RNH1 (HGNC:10074): (ribonuclease/angiogenin inhibitor 1) Placental ribonuclease inhibitor (PRI) is a member of a family of proteinaceous cytoplasmic RNase inhibitors that occur in many tissues and bind to both intracellular and extracellular RNases (summarized by Lee et al., 1988 [PubMed 3219362]). In addition to control of intracellular RNases, the inhibitor may have a role in the regulation of angiogenin (MIM 105850). Ribonuclease inhibitor, of 50,000 Da, binds to ribonucleases and holds them in a latent form. Since neutral and alkaline ribonucleases probably play a critical role in the turnover of RNA in eukaryotic cells, RNH may be essential for control of mRNA turnover; the interaction of eukaryotic cells with ribonuclease may be reversible in vivo.[supplied by OMIM, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.863
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNH1 | NM_203387.3 | c.626G>A | p.Cys209Tyr | missense_variant | 7/11 | ENST00000354420.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNH1 | ENST00000354420.7 | c.626G>A | p.Cys209Tyr | missense_variant | 7/11 | 5 | NM_203387.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000444 AC: 11AN: 247524Hom.: 0 AF XY: 0.0000669 AC XY: 9AN XY: 134616
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GnomAD4 exome AF: 0.0000411 AC: 60AN: 1460152Hom.: 0 Cov.: 35 AF XY: 0.0000496 AC XY: 36AN XY: 726324
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152236Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74380
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1Other: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 | Jan 23, 2023 | The c.626G>A (p.C209Y) alteration is located in exon 7 (coding exon 5) of the RNH1 gene. This alteration results from a G to A substitution at nucleotide position 626, causing the cysteine (C) at amino acid position 209 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Encephalitis, acute, infection-induced, susceptibility to, 12 Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Aug 10, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
T;T;T;T;T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H;H;H;.;H;H;H;H
MutationTaster
Benign
N;N;N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D
Polyphen
D;D;D;D;.;D;D;D;D
Vest4
MVP
MPC
ClinPred
D
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