Variant 11-494945-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_203387.3(RNH1):c.1236C>A(p.Asp412Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

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: -1.49

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.079443306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNH1	NM_203387.3 linkuse as main transcript	c.1236C>A	p.Asp412Glu	missense_variant	10/11	ENST00000354420.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNH1	ENST00000354420.7 linkuse as main transcript	c.1236C>A	p.Asp412Glu	missense_variant	10/11	5	NM_203387.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000849

AC:

AN:

235592

Hom.:

AF XY:

0.00000781

AC XY:

AN XY:

128096

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000678

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1455714

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723710

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:

0.0000468

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

AC:

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

Feb 14, 2024

The c.1236C>A (p.D412E) alteration is located in exon 10 (coding exon 8) of the RNH1 gene. This alteration results from a C to A substitution at nucleotide position 1236, causing the aspartic acid (D) at amino acid position 412 to be replaced by a glutamic acid (E). 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

Benign

0.28

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.0

DANN

Benign

0.66

DEOGEN2

Benign

0.062

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

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.54

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

M_CAP

Benign

0.062

MetaRNN

Benign

0.079

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

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.0

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.0

N;N;N;N;D;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.071

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

Sift4G

Benign

0.12

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

Polyphen

0.0090

B;B;B;B;.;B;B;B;B

Vest4

0.093

MutPred

0.46

Loss of catalytic residue at G414 (P = 0.1683);Loss of catalytic residue at G414 (P = 0.1683);Loss of catalytic residue at G414 (P = 0.1683);Loss of catalytic residue at G414 (P = 0.1683);.;Loss of catalytic residue at G414 (P = 0.1683);Loss of catalytic residue at G414 (P = 0.1683);Loss of catalytic residue at G414 (P = 0.1683);Loss of catalytic residue at G414 (P = 0.1683);

MVP

0.42

MPC

0.14

ClinPred

0.046

GERP RS

-2.9

Varity_R

0.24

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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