chr9-122859083-T-TG
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001100588.3(RC3H2):c.1868_1869insC(p.Thr624AsnfsTer18) variant causes a frameshift change. 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: 33)
Consequence
RC3H2
NM_001100588.3 frameshift
NM_001100588.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.22
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RC3H2 | NM_001100588.3 | c.1868_1869insC | p.Thr624AsnfsTer18 | frameshift_variant | 12/21 | ENST00000357244.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RC3H2 | ENST00000357244.7 | c.1868_1869insC | p.Thr624AsnfsTer18 | frameshift_variant | 12/21 | 5 | NM_001100588.3 | P1 | |
RC3H2 | ENST00000373670.5 | c.1868_1869insC | p.Thr624AsnfsTer18 | frameshift_variant | 11/20 | 5 | P1 | ||
RC3H2 | ENST00000423239.6 | c.1868_1869insC | p.Thr624AsnfsTer18 | frameshift_variant | 12/18 | 5 | |||
RC3H2 | ENST00000498479.5 | c.*349_*350insC | 3_prime_UTR_variant, NMD_transcript_variant | 13/22 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Mar 12, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.