chr9-4793179-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005772.5(RCL1):c.88G>C(p.Val30Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,610,434 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 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
RCL1
NM_005772.5 missense
NM_005772.5 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 4.42
Genes affected
RCL1 (HGNC:17687): (RNA terminal phosphate cyclase like 1) Predicted to enable endoribonuclease activity. Predicted to be involved in endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to act upstream of or within endonucleolytic cleavage in 5'-ETS of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) and endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleoplasm. Predicted to be active in nucleolus. [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.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.23073784).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RCL1 | NM_005772.5 | c.88G>C | p.Val30Leu | missense_variant | 1/9 | ENST00000381750.9 | |
RCL1 | NM_001286699.2 | c.-139G>C | 5_prime_UTR_variant | 1/7 | |||
RCL1 | NM_001286700.2 | c.-211G>C | 5_prime_UTR_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RCL1 | ENST00000381750.9 | c.88G>C | p.Val30Leu | missense_variant | 1/9 | 1 | NM_005772.5 | P1 | |
RCL1 | ENST00000381732.3 | c.88G>C | p.Val30Leu | missense_variant | 1/3 | 2 | |||
RCL1 | ENST00000442869.5 | c.-211G>C | 5_prime_UTR_variant | 1/8 | 3 | ||||
RCL1 | ENST00000473230.1 | n.93G>C | non_coding_transcript_exon_variant | 1/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000206 AC: 5AN: 242896Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131742
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GnomAD4 exome AF: 0.0000247 AC: 36AN: 1458140Hom.: 0 Cov.: 29 AF XY: 0.0000248 AC XY: 18AN XY: 725158
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152294Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74472
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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 | Jul 05, 2023 | The c.88G>C (p.V30L) alteration is located in exon 1 (coding exon 1) of the RCL1 gene. This alteration results from a G to C substitution at nucleotide position 88, causing the valine (V) at amino acid position 30 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
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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