rs1553121852
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM4_SupportingPP5
The NM_000975.5(RPL11):c.296_298del(p.Phe99del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
RPL11
NM_000975.5 inframe_deletion
NM_000975.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.79
Genes affected
RPL11 (HGNC:10301): (ribosomal protein L11) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L5P family of ribosomal proteins. It is located in the cytoplasm. The protein probably associates with the 5S rRNA. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
?
In a chain 60S ribosomal protein L11 (size 176) in uniprot entity RL11_HUMAN there are 10 pathogenic changes around while only 0 benign (100%) in NM_000975.5
PM4
?
Nonframeshift variant in NON repetitive region in NM_000975.5. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 1-23694688-ACTT-A is Pathogenic according to our data. Variant chr1-23694688-ACTT-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 436550.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Likely_pathogenic=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL11 | NM_000975.5 | c.296_298del | p.Phe99del | inframe_deletion | 4/6 | ENST00000643754.2 | |
RPL11 | NM_001199802.1 | c.293_295del | p.Phe98del | inframe_deletion | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL11 | ENST00000643754.2 | c.296_298del | p.Phe99del | inframe_deletion | 4/6 | NM_000975.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Diamond-Blackfan anemia Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 15, 2023 | This variant, c.296_298del, results in the deletion of 1 amino acid(s) of the RPL11 protein (p.Phe99del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Diamond-Blackfan anemia (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 436550). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 28, 2016 | - - |
Computational scores
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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