11-502069-C-T

Variant names:

• chr11-502069-C-T
• NM_203387.3:c.94G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203387.3(RNH1):​c.94G>A​(p.Val32Met) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNH1 NM_203387.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.29
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• encephalitis, acute, infection-induced, susceptibility to, 12

  Inheritance: AR Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22981352).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203387.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNH1	NM_203387.3	MANE Select	c.94G>A	p.Val32Met	missense	Exon 3 of 11	NP_976321.1	A0A140VJT8
	RNH1	NM_002939.4		c.94G>A	p.Val32Met	missense	Exon 3 of 11	NP_002930.2
	RNH1	NM_203383.2		c.94G>A	p.Val32Met	missense	Exon 3 of 11	NP_976317.1	P13489

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNH1	ENST00000354420.7	TSL:5 MANE Select	c.94G>A	p.Val32Met	missense	Exon 3 of 11	ENSP00000346402.2	P13489
	RNH1	ENST00000356187.9	TSL:1	c.94G>A	p.Val32Met	missense	Exon 2 of 10	ENSP00000348515.5	P13489
	RNH1	ENST00000397604.7	TSL:1	c.94G>A	p.Val32Met	missense	Exon 2 of 10	ENSP00000380729.3	P13489

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.3
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Benign	0.034	D
Sift4G	Uncertain	0.049	D
Polyphen		0.99	D
Vest4		0.25
MutPred		0.37		Loss of sheet (P = 0.0817)
MVP		0.54
MPC		0.56
ClinPred		0.48	T
GERP RS		1.6
Varity_R		0.13
gMVP		0.33
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr11-502069;