9-122849799-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001100588.3(RC3H2):c.3404C>G(p.Pro1135Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000447 in 1,566,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
RC3H2
NM_001100588.3 missense
NM_001100588.3 missense
Scores
2
6
9
Clinical Significance
Conservation
PhyloP100: 6.41
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 Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RC3H2 | NM_001100588.3 | c.3404C>G | p.Pro1135Arg | missense_variant | 21/21 | ENST00000357244.7 | |
RC3H2 | NM_001354482.2 | c.3290C>G | p.Pro1097Arg | missense_variant | 20/20 | ||
RC3H2 | NM_001354479.2 | c.3233C>G | p.Pro1078Arg | missense_variant | 20/20 | ||
RC3H2 | NM_001354478.2 | c.3385C>G | p.Arg1129Gly | missense_variant | 21/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RC3H2 | ENST00000357244.7 | c.3404C>G | p.Pro1135Arg | missense_variant | 21/21 | 5 | NM_001100588.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151978Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000142 AC: 3AN: 211252Hom.: 0 AF XY: 0.0000173 AC XY: 2AN XY: 115658
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GnomAD4 exome AF: 0.00000353 AC: 5AN: 1414902Hom.: 0 Cov.: 31 AF XY: 0.00000427 AC XY: 3AN XY: 703246
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151978Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74206
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 25, 2022 | The c.3404C>G (p.P1135R) alteration is located in exon 21 (coding exon 20) of the RC3H2 gene. This alteration results from a C to G substitution at nucleotide position 3404, causing the proline (P) at amino acid position 1135 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at