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11-498935-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_203387.3(RNH1):c.615-2A>C variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: not found (cov: 34)

Consequence

RNH1
NM_203387.3 splice_acceptor

Scores

1
1
5
Splicing: ADA: 1.000
2

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 3.43
Variant links:
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.

PVS1
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.06132756 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNH1NM_203387.3 linkuse as main transcriptc.615-2A>C splice_acceptor_variant ENST00000354420.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNH1ENST00000354420.7 linkuse as main transcriptc.615-2A>C splice_acceptor_variant 5 NM_203387.3 P1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
34

ClinVar

Significance: risk factor
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Encephalitis, acute, infection-induced, susceptibility to, 12 Other:1
risk factor, no assertion criteria providedliterature onlyOMIMAug 10, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.019
T
BayesDel_noAF
Benign
-0.26
Cadd
Pathogenic
28
Dann
Benign
0.93
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Benign
0.75
D
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D
GERP RS
3.4

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.78
SpliceAI score (max)
0.99
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.76
Position offset: -9
DS_AL_spliceai
0.99
Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-498935; API