rs1555841379
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_001022.4(RPS19):c.356+3A>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
RPS19
NM_001022.4 splice_donor_region, intron
NM_001022.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.9981
2
Clinical Significance
Conservation
PhyloP100: 0.624
Genes affected
RPS19 (HGNC:10402): (ribosomal protein S19) 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 S19E family of ribosomal proteins. It is located in the cytoplasm. Mutations in this gene cause Diamond-Blackfan anemia (DBA), a constitutional erythroblastopenia characterized by absent or decreased erythroid precursors, in a subset of patients. This suggests a possible extra-ribosomal function for this gene in erythropoietic differentiation and proliferation, in addition to its ribosomal function. Higher expression levels of this gene in some primary colon carcinomas compared to matched normal colon tissues has been observed. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 19-41869217-A-C is Pathogenic according to our data. Variant chr19-41869217-A-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 436553.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-41869217-A-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPS19 | NM_001022.4 | c.356+3A>C | splice_donor_region_variant, intron_variant | ENST00000598742.6 | |||
RPS19 | NM_001321483.2 | c.356+3A>C | splice_donor_region_variant, intron_variant | ||||
RPS19 | NM_001321484.2 | c.356+3A>C | splice_donor_region_variant, intron_variant | ||||
RPS19 | NM_001321485.2 | c.369+3A>C | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPS19 | ENST00000598742.6 | c.356+3A>C | splice_donor_region_variant, intron_variant | 1 | NM_001022.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Diamond-Blackfan anemia 1 Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 21, 2021 | DNA sequence analysis of the RPS19 gene in demonstrated a sequence change located near the canonical splice donor site in intron 4, c.356+3A>C. This sequence change does not appear to have been previously described in patients with RPS19-related disorders and has also not been described as a known benign sequence change in the RPS19 gene. Based on in silico splice prediction programs, this sequence change likely affects normal splicing of the RPS19 gene, which would result in an abnormal protein, however functional studies have not been performed to prove this conclusively. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 6
DS_DL_spliceai
Position offset: -3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at