rs267607022
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001014.5(RPS10):c.337C>T(p.Arg113Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Consequence
RPS10
NM_001014.5 stop_gained
NM_001014.5 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 5.59
Genes affected
RPS10 (HGNC:10383): (ribosomal protein S10) 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 40S subunit. The protein belongs to the S10E family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternate splicing results in multiple transcript variants that encode the same protein. Naturally occurring read-through transcription occurs between this locus and the neighboring locus NUDT3 (nudix (nucleoside diphosphate linked moiety X)-type motif 3).[provided by RefSeq, Feb 2011]
Genome browser will be placed here
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 6-34421793-G-A is Pathogenic according to our data. Variant chr6-34421793-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 6187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-34421793-G-A is described in Lovd as [Pathogenic]. Variant chr6-34421793-G-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPS10 | NM_001014.5 | c.337C>T | p.Arg113Ter | stop_gained | 4/6 | ENST00000648437.1 | |
RPS10-NUDT3 | NM_001202470.3 | c.337C>T | p.Arg113Ter | stop_gained | 4/9 | ||
RPS10 | NM_001203245.3 | c.337C>T | p.Arg113Ter | stop_gained | 4/6 | ||
RPS10 | NM_001204091.2 | c.337C>T | p.Arg113Ter | stop_gained | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPS10 | ENST00000648437.1 | c.337C>T | p.Arg113Ter | stop_gained | 4/6 | NM_001014.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Diamond-Blackfan anemia Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2021 | This sequence change creates a premature translational stop signal (p.Arg113*) in the RPS10 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RPS10 are known to be pathogenic (PMID: 20116044, 23718193). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 6187). This premature translational stop signal has been observed in individual(s) with Diamond-Blackfan anemia (PMID: 20116044). This variant is not present in population databases (ExAC no frequency). - |
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 14, 2019 | The p.R113* pathogenic mutation (also known as c.337C>T), located in coding exon 3 of the RPS10 gene, results from a C to T substitution at nucleotide position 337. This changes the amino acid from an arginine to a stop codon within coding exon 3. This mutation was identified in multiple individuals with Diamond-Blackfan anemia (Doherty L et al. Am. J. Hum. Genet., 2010 Feb;86:222-8; Gerrard G et al. Br. J. Haematol., 2013 Aug;162:530-6). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
Diamond-Blackfan anemia 9 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 01, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
0.96, 0.97
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at