9-122858721-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001100588.3(RC3H2):c.2231C>T(p.Ser744Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,613,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
RC3H2
NM_001100588.3 missense
NM_001100588.3 missense
Scores
1
3
13
Clinical Significance
Conservation
PhyloP100: 6.46
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 Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.34340268).
BS2
?
High AC in GnomAdExome at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RC3H2 | NM_001100588.3 | c.2231C>T | p.Ser744Leu | missense_variant | 12/21 | ENST00000357244.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RC3H2 | ENST00000357244.7 | c.2231C>T | p.Ser744Leu | missense_variant | 12/21 | 5 | NM_001100588.3 | P1 | |
RC3H2 | ENST00000373670.5 | c.2231C>T | p.Ser744Leu | missense_variant | 11/20 | 5 | P1 | ||
RC3H2 | ENST00000423239.6 | c.2231C>T | p.Ser744Leu | missense_variant | 12/18 | 5 | |||
RC3H2 | ENST00000498479.5 | c.*712C>T | 3_prime_UTR_variant, NMD_transcript_variant | 13/22 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152260Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000201 AC: 5AN: 249066Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135156
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GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461326Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 726958
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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 | Nov 13, 2023 | The c.2231C>T (p.S744L) alteration is located in exon 12 (coding exon 11) of the RC3H2 gene. This alteration results from a C to T substitution at nucleotide position 2231, causing the serine (S) at amino acid position 744 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
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MVP
MPC
ClinPred
T
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