Variant 11-498526-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_203387.3(RNH1):c.887T>C(p.Leu296Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,030 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RNH1
NM_203387.3 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 1.68

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]

RNH1 links:

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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
RNH1	NM_203387.3 linkuse as main transcript	c.887T>C	p.Leu296Pro	missense_variant	8/11	ENST00000354420.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNH1	ENST00000354420.7 linkuse as main transcript	c.887T>C	p.Leu296Pro	missense_variant	8/11	5	NM_203387.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461030

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726820

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 provided

literature only

OMIM

Aug 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T;T;T;T;T;T;T;T

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.68

.;T;.;.;T;.;.;.;.

M_CAP

Uncertain

0.091

MetaRNN

Uncertain

0.59

D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.40

MutationAssessor

Uncertain

2.0

M;M;M;M;.;M;M;M;M

MutationTaster

Benign

0.62

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.1

D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.40

Sift

Benign

0.069

T;T;T;T;D;T;T;T;T

Sift4G

Uncertain

0.0020

D;D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;.;D;D;D;D

Vest4

0.78

MutPred

0.60

Loss of stability (P = 0.0194);Loss of stability (P = 0.0194);Loss of stability (P = 0.0194);Loss of stability (P = 0.0194);.;Loss of stability (P = 0.0194);Loss of stability (P = 0.0194);Loss of stability (P = 0.0194);Loss of stability (P = 0.0194);

MVP

0.81

MPC

0.81

ClinPred

0.99

GERP RS

3.7

Varity_R

0.92

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over