11-498116-C-G

Variant names:

• chr11-498116-C-G
• rs750626202
• NM_203387.3:c.982G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_203387.3(RNH1):​c.982G>C​(p.Ala328Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A328T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 35)
• Consequence: RNH1 NM_203387.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36775482).

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.982G>C	p.Ala328Pro	missense	Exon 9 of 11	NP_976321.1	A0A140VJT8
	RNH1	NM_002939.4		c.982G>C	p.Ala328Pro	missense	Exon 9 of 11	NP_002930.2
	RNH1	NM_203383.2		c.982G>C	p.Ala328Pro	missense	Exon 9 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.982G>C	p.Ala328Pro	missense	Exon 9 of 11	ENSP00000346402.2	P13489
	RNH1	ENST00000356187.9	TSL:1	c.982G>C	p.Ala328Pro	missense	Exon 8 of 10	ENSP00000348515.5	P13489
	RNH1	ENST00000397604.7	TSL:1	c.982G>C	p.Ala328Pro	missense	Exon 8 of 10	ENSP00000380729.3	P13489

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.027
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.035
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.21
Sift	Benign	0.039	D
Sift4G	Benign	0.16	T
Polyphen		0.99	D
Vest4		0.46
MutPred		0.55		Gain of helix (P = 0.062)
MVP		0.78
MPC		0.66
ClinPred		0.96	D
GERP RS		2.8
Varity_R		0.86
gMVP		0.54
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs750626202; hg19: chr11-498116;