chr11-499992-T-G

Variant names:

• chr11-499992-T-G
• rs773849440
• NM_203387.3:c.280A>C

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.280A>C​(p.Asn94His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000778 in 1,414,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000078 (0 hom.)
• Consequence: RNH1 NM_203387.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00600
• 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=0.10881111).

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.280A>C	p.Asn94His	missense	Exon 5 of 11	NP_976321.1	A0A140VJT8
	RNH1	NM_002939.4		c.280A>C	p.Asn94His	missense	Exon 5 of 11	NP_002930.2
	RNH1	NM_203383.2		c.280A>C	p.Asn94His	missense	Exon 5 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.280A>C	p.Asn94His	missense	Exon 5 of 11	ENSP00000346402.2	P13489
	RNH1	ENST00000356187.9	TSL:1	c.280A>C	p.Asn94His	missense	Exon 4 of 10	ENSP00000348515.5	P13489
	RNH1	ENST00000397604.7	TSL:1	c.280A>C	p.Asn94His	missense	Exon 4 of 10	ENSP00000380729.3	P13489

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000229 AC: 4 AN: 174420 AF XY: 0.0000106

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000778 AC: 11 AN: 1414034 Hom.: 0 Cov.: 32 AF XY: 0.00000857 AC XY: 6 AN XY: 699942

African (AFR) AF: 0.00 AC: 0 AN: 32382

American (AMR) AF: 0.00 AC: 0 AN: 37868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24898

East Asian (EAS) AF: 0.00 AC: 0 AN: 37216

South Asian (SAS) AF: 0.000136 AC: 11 AN: 81076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089576

Other (OTH) AF: 0.00 AC: 0 AN: 58504

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000254 AC: 3

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	0.24
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.88
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.0060
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.067
Sift	Benign	0.034	D
Sift4G	Benign	0.083	T
Polyphen		0.91	P
Vest4		0.32
MutPred		0.40		Loss of sheet (P = 0.0817)
MVP		0.53
MPC		0.34
ClinPred		0.11	T
GERP RS		0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.44
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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

dbSNP: rs773849440; hg19: chr11-499992;