chr9-4827014-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005772.5(RCL1):c.365A>G(p.Asn122Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,614,074 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 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
RCL1
NM_005772.5 missense
NM_005772.5 missense
Scores
5
7
7
Clinical Significance
Conservation
PhyloP100: 8.91
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.785
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RCL1 | NM_005772.5 | c.365A>G | p.Asn122Ser | missense_variant | 3/9 | ENST00000381750.9 | |
RCL1 | NM_001286699.2 | c.-90-6140A>G | intron_variant | ||||
RCL1 | NM_001286700.2 | c.-91+3395A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RCL1 | ENST00000381750.9 | c.365A>G | p.Asn122Ser | missense_variant | 3/9 | 1 | NM_005772.5 | P1 | |
RCL1 | ENST00000381732.3 | c.365A>G | p.Asn122Ser | missense_variant | 3/3 | 2 | |||
RCL1 | ENST00000442869.5 | c.-91+3395A>G | intron_variant | 3 | |||||
RCL1 | ENST00000473230.1 | n.213+3395A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152182Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251460Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135910
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GnomAD4 exome AF: 0.000140 AC: 204AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.000143 AC XY: 104AN XY: 727248
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GnomAD4 genome ? AF: 0.000151 AC: 23AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74342
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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 | Jan 07, 2022 | The c.365A>G (p.N122S) alteration is located in exon 3 (coding exon 3) of the RCL1 gene. This alteration results from a A to G substitution at nucleotide position 365, causing the asparagine (N) at amino acid position 122 to be replaced by a serine (S). 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;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;T
Sift4G
Benign
T;D
Polyphen
D;.
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