chr11-498598-C-T

Variant names:

• chr11-498598-C-T
• rs923282852
• NM_203387.3:c.815G>A

Variant summary

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

The NM_203387.3(RNH1):​c.815G>A​(p.Gly272Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,460,434 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: RNH1 NM_203387.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.53
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.815G>A	p.Gly272Asp	missense	Exon 8 of 11	NP_976321.1	A0A140VJT8
	RNH1	NM_002939.4		c.815G>A	p.Gly272Asp	missense	Exon 8 of 11	NP_002930.2
	RNH1	NM_203383.2		c.815G>A	p.Gly272Asp	missense	Exon 8 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.815G>A	p.Gly272Asp	missense	Exon 8 of 11	ENSP00000346402.2	P13489
	RNH1	ENST00000356187.9	TSL:1	c.815G>A	p.Gly272Asp	missense	Exon 7 of 10	ENSP00000348515.5	P13489
	RNH1	ENST00000397604.7	TSL:1	c.815G>A	p.Gly272Asp	missense	Exon 7 of 10	ENSP00000380729.3	P13489

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1460434 Hom.: 0 Cov.: 34 AF XY: 0.00000826 AC XY: 6 AN XY: 726550

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 34

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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		3.5
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.029	D
Sift4G	Benign	0.062	T
Polyphen		1.0	D
Vest4		0.58
MutPred		0.54		Gain of ubiquitination at K271 (P = 0.0872)
MVP		0.83
MPC		0.70
ClinPred		0.98	D
GERP RS		3.7
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.77
gMVP		0.52
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs923282852; hg19: chr11-498598;