chr9-4860138-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005772.5(RCL1):c.985C>T(p.Arg329Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000892 in 1,570,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000092 ( 0 hom. )
Consequence
RCL1
NM_005772.5 missense
NM_005772.5 missense
Scores
10
6
3
Clinical Significance
Conservation
PhyloP100: 3.60
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.794
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RCL1 | NM_005772.5 | c.985C>T | p.Arg329Trp | missense_variant | 9/9 | ENST00000381750.9 | |
RCL1 | NM_001286699.2 | c.511C>T | p.Arg171Trp | missense_variant | 7/7 | ||
RCL1 | NM_001286700.2 | c.511C>T | p.Arg171Trp | missense_variant | 8/8 | ||
RCL1 | NM_001286701.2 | c.427C>T | p.Arg143Trp | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RCL1 | ENST00000381750.9 | c.985C>T | p.Arg329Trp | missense_variant | 9/9 | 1 | NM_005772.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000594 AC: 9AN: 151582Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000970 AC: 22AN: 226748Hom.: 0 AF XY: 0.000130 AC XY: 16AN XY: 123230
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GnomAD4 exome AF: 0.0000923 AC: 131AN: 1418738Hom.: 0 Cov.: 30 AF XY: 0.000105 AC XY: 74AN XY: 704322
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GnomAD4 genome ? AF: 0.0000594 AC: 9AN: 151582Hom.: 0 Cov.: 32 AF XY: 0.0000541 AC XY: 4AN XY: 73976
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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 29, 2022 | The c.985C>T (p.R329W) alteration is located in exon 9 (coding exon 9) of the RCL1 gene. This alteration results from a C to T substitution at nucleotide position 985, causing the arginine (R) at amino acid position 329 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;.;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
D;.;.;.;.
Vest4
MVP
MPC
ClinPred
D
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