9-122858788-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001100588.3(RC3H2):c.2164G>T(p.Val722Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
RC3H2
NM_001100588.3 missense
NM_001100588.3 missense
Scores
1
6
10
Clinical Significance
Conservation
PhyloP100: 5.13
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 2 ACMG points.
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.2164G>T | p.Val722Leu | missense_variant | 12/21 | ENST00000357244.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RC3H2 | ENST00000357244.7 | c.2164G>T | p.Val722Leu | missense_variant | 12/21 | 5 | NM_001100588.3 | P1 | |
RC3H2 | ENST00000373670.5 | c.2164G>T | p.Val722Leu | missense_variant | 11/20 | 5 | P1 | ||
RC3H2 | ENST00000423239.6 | c.2164G>T | p.Val722Leu | missense_variant | 12/18 | 5 | |||
RC3H2 | ENST00000498479.5 | c.*645G>T | 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
Asia WGS
AF:
AC:
1
AN:
3478
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 | Sep 27, 2022 | The c.2164G>T (p.V722L) alteration is located in exon 12 (coding exon 11) of the RC3H2 gene. This alteration results from a G to T substitution at nucleotide position 2164, causing the valine (V) at amino acid position 722 to be replaced by a leucine (L). 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
Uncertain
D
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift4G
Benign
T;T;T
Polyphen
P;P;P
Vest4
MutPred
Gain of phosphorylation at S725 (P = 0.2036);Gain of phosphorylation at S725 (P = 0.2036);Gain of phosphorylation at S725 (P = 0.2036);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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