rs1555208596
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001029.5(RPS26):c.224_225del(p.Val75GlufsTer15) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
RPS26
NM_001029.5 frameshift
NM_001029.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.66
Genes affected
RPS26 (HGNC:10414): (ribosomal protein S26) This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S26E family of ribosomal proteins. Mutations in this gene are found in Diamond-Blackfan anemia 10. There are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 12-56043400-CTG-C is Pathogenic according to our data. Variant chr12-56043400-CTG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 470476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPS26 | NM_001029.5 | c.224_225del | p.Val75GlufsTer15 | frameshift_variant | 3/4 | ENST00000646449.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPS26 | ENST00000646449.2 | c.224_225del | p.Val75GlufsTer15 | frameshift_variant | 3/4 | NM_001029.5 | P1 | ||
RPS26 | ENST00000356464.10 | c.224_225del | p.Val75GlufsTer15 | frameshift_variant | 4/5 | 1 | P1 | ||
RPS26 | ENST00000552361.1 | c.224_225del | p.Val75GlufsTer15 | frameshift_variant | 4/5 | 5 | P1 | ||
RPS26 | ENST00000548590.1 | n.1011_1012del | non_coding_transcript_exon_variant | 2/3 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Diamond-Blackfan anemia 10 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Nov 20, 2018 | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | This sequence change creates a premature translational stop signal (p.Val75Glufs*15) in the RPS26 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 41 amino acid(s) of the RPS26 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RPS26-related conditions. ClinVar contains an entry for this variant (Variation ID: 470476). 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. - |
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