9-122849798-CGG-TAA

Variant names:

• chr9-122849798-CGG-TAA
• NM_001100588.3:c.3403_3405delCCGinsTTA
• RC3H2 p.Pro1135Leu

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

The NM_001354478.2(RC3H2):​c.3384_3386delCCGinsTTA​(p.Arg1129*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RC3H2 NM_001354478.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.41
• Publications: 0 publications found

Genes affected

RC3H2 (HGNC:21461): (ring finger and CCCH-type domains 2) Enables nucleic acid binding activity and ubiquitin protein ligase activity. Involved in protein polyubiquitination. Located in cell surface; intracellular membrane-bounded organelle; and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354478.2. 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
	RC3H2	NM_001100588.3	MANE Select	c.3403_3405delCCGinsTTA	p.Pro1135Leu	missense	N/A	NP_001094058.1	Q9HBD1-1
	RC3H2	NM_001354478.2		c.3384_3386delCCGinsTTA	p.Arg1129*	stop_gained	N/A	NP_001341407.1
	RC3H2	NM_001354482.2		c.3289_3291delCCGinsTTA	p.Pro1097Leu	missense	N/A	NP_001341411.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RC3H2	ENST00000357244.7	TSL:5 MANE Select	c.3403_3405delCCGinsTTA	p.Pro1135Leu	missense	N/A	ENSP00000349783.2	Q9HBD1-1
	RC3H2	ENST00000454740.5	TSL:5	c.558_560delCCGinsTTA	p.Arg187*	stop_gained	N/A	ENSP00000398081.1	H0Y5D9
	RC3H2	ENST00000373670.5	TSL:5	c.3403_3405delCCGinsTTA	p.Pro1135Leu	missense	N/A	ENSP00000362774.1	Q9HBD1-1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-125612077;