Variant 11-494771-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_203387.3(RNH1):c.1306G>A(p.Asp436Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RNH1
NM_203387.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90

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:

RNH1 (HGNC:):

RNH1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39095137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNH1	NM_203387.3 linkuse as main transcript	c.1306G>A	p.Asp436Asn	missense_variant	11/11	ENST00000354420.7	NP_976321.1	P13489A0A140VJT8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNH1	ENST00000354420.7 linkuse as main transcript	c.1306G>A	p.Asp436Asn	missense_variant	11/11	5	NM_203387.3	ENSP00000346402.2		P13489

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249526

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135060

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Aug 10, 2024

The c.1306G>A (p.D436N) alteration is located in exon 11 (coding exon 9) of the RNH1 gene. This alteration results from a G to A substitution at nucleotide position 1306, causing the aspartic acid (D) at amino acid position 436 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.075

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

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.79

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

M_CAP

Benign

0.039

MetaRNN

Benign

0.39

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

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.7

M;M;M;M;M;M;M;M

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.6

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

REVEL

Benign

0.18

Sift

Uncertain

0.019

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

Sift4G

Benign

0.37

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

Polyphen

1.0

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

Vest4

0.46

MutPred

0.52

Loss of phosphorylation at Y438 (P = 0.1256);Loss of phosphorylation at Y438 (P = 0.1256);Loss of phosphorylation at Y438 (P = 0.1256);Loss of phosphorylation at Y438 (P = 0.1256);Loss of phosphorylation at Y438 (P = 0.1256);Loss of phosphorylation at Y438 (P = 0.1256);Loss of phosphorylation at Y438 (P = 0.1256);Loss of phosphorylation at Y438 (P = 0.1256);

MVP

0.69

MPC

0.62

ClinPred

0.78

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.46

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over