11-498863-GCGA-TGCCCAAGGCCCAG

Variant names:

• chr11-498863-GCGA-TGCCCAAGGCCCAG
• rs1849424627
• NM_203387.3:c.682_685delTCGCinsCTGGGCCTTGGGCA

Variant summary

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

The NM_203387.3(RNH1):​c.682_685delTCGCinsCTGGGCCTTGGGCA​(p.Ser228LeufsTer17) variant causes a frameshift, missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 34)
• Consequence: RNH1 NM_203387.3 frameshift, missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 O:1
• Conservation: PhyloP100: 1.76
• Publications: 1 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.682_685delTCGCinsCTGGGCCTTGGGCA	p.Ser228LeufsTer17	frameshift missense	Exon 7 of 11	NP_976321.1	A0A140VJT8
	RNH1	NM_002939.4		c.682_685delTCGCinsCTGGGCCTTGGGCA	p.Ser228LeufsTer17	frameshift missense	Exon 7 of 11	NP_002930.2
	RNH1	NM_203383.2		c.682_685delTCGCinsCTGGGCCTTGGGCA	p.Ser228LeufsTer17	frameshift missense	Exon 7 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.682_685delTCGCinsCTGGGCCTTGGGCA	p.Ser228LeufsTer17	frameshift missense	Exon 7 of 11	ENSP00000346402.2	P13489
	RNH1	ENST00000356187.9	TSL:1	c.682_685delTCGCinsCTGGGCCTTGGGCA	p.Ser228LeufsTer17	frameshift missense	Exon 6 of 10	ENSP00000348515.5	P13489
	RNH1	ENST00000397604.7	TSL:1	c.682_685delTCGCinsCTGGGCCTTGGGCA	p.Ser228LeufsTer17	frameshift missense	Exon 6 of 10	ENSP00000380729.3	P13489

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	RNH1-related disorder (1)
-	-	-	Encephalitis, acute, infection-induced, susceptibility to, 12 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs1849424627; hg19: chr11-498863;