chr9-4833202-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005772.5(RCL1):āc.433A>Cā(p.Ile145Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000104 in 1,612,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000098 ( 0 hom., cov: 32)
Exomes š: 0.00010 ( 0 hom. )
Consequence
RCL1
NM_005772.5 missense
NM_005772.5 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 5.91
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=0.13045713).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RCL1 | NM_005772.5 | c.433A>C | p.Ile145Leu | missense_variant | 4/9 | ENST00000381750.9 | |
RCL1 | NM_001286699.2 | c.-42A>C | 5_prime_UTR_variant | 2/7 | |||
RCL1 | NM_001286700.2 | c.-42A>C | 5_prime_UTR_variant | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RCL1 | ENST00000381750.9 | c.433A>C | p.Ile145Leu | missense_variant | 4/9 | 1 | NM_005772.5 | P1 | |
RCL1 | ENST00000442869.5 | c.-42A>C | 5_prime_UTR_variant | 3/8 | 3 | ||||
RCL1 | ENST00000473230.1 | n.262A>C | non_coding_transcript_exon_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152204Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251434Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135896
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GnomAD4 exome AF: 0.000104 AC: 152AN: 1460658Hom.: 0 Cov.: 28 AF XY: 0.000110 AC XY: 80AN XY: 726774
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GnomAD4 genome AF: 0.0000985 AC: 15AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74482
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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 | Sep 17, 2021 | The c.433A>C (p.I145L) alteration is located in exon 4 (coding exon 4) of the RCL1 gene. This alteration results from a A to C substitution at nucleotide position 433, causing the isoleucine (I) at amino acid position 145 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
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
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