11-497981-G-C

Variant names:

• chr11-497981-G-C
• rs759267447
• NM_203387.3:c.1117C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_203387.3(RNH1):​c.1117C>G​(p.Arg373Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 35)
• Consequence: RNH1 NM_203387.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNH1	NM_203387.3	c.1117C>G	p.Arg373Gly	missense_variant	Exon 9 of 11	ENST00000354420.7	NP_976321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNH1	ENST00000354420.7	c.1117C>G	p.Arg373Gly	missense_variant	Exon 9 of 11	5	NM_203387.3	ENSP00000346402.2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 35

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Uncertain	0.43	T;T;T;T;T;T;T;T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.72	.;T;.;.;T;.;.;.;.
M_CAP	Uncertain	0.096	D
MetaRNN	Uncertain	0.44	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.4	M;M;M;M;.;M;M;M;M
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.8	D;D;D;D;D;D;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.013	D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.049	D;D;D;D;T;D;D;D;D
Polyphen		0.96	D;D;D;D;.;D;D;D;D
Vest4		0.46
MutPred		0.57		Gain of catalytic residue at V374 (P = 0.015);Gain of catalytic residue at V374 (P = 0.015);Gain of catalytic residue at V374 (P = 0.015);Gain of catalytic residue at V374 (P = 0.015);.;Gain of catalytic residue at V374 (P = 0.015);Gain of catalytic residue at V374 (P = 0.015);Gain of catalytic residue at V374 (P = 0.015);Gain of catalytic residue at V374 (P = 0.015);
MVP		0.66
MPC		0.63
ClinPred		0.90	D
GERP RS		2.8
Varity_R		0.30
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs759267447; hg19: chr11-497981;