19-1440069-G-C
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001018.5(RPS15):āc.140G>Cā(p.Arg47Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000797 in 150,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.000080 ( 0 hom., cov: 32)
Exomes š: 0.11 ( 1 hom. )
Failed GnomAD Quality Control
Consequence
RPS15
NM_001018.5 missense
NM_001018.5 missense
Scores
5
2
9
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
RPS15 (HGNC:10388): (ribosomal protein S15) 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 S19P family of ribosomal proteins. It is located in the cytoplasm. This gene has been found to be activated in various tumors, such as insulinomas, esophageal cancers, and colon cancers. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.002413988).
BP6
Variant 19-1440069-G-C is Benign according to our data. Variant chr19-1440069-G-C is described in ClinVar as [Benign]. Clinvar id is 440242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-1440069-G-C is described in Lovd as [Likely_benign].
BS2
High AC in GnomAd4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RPS15 | NM_001018.5 | c.140G>C | p.Arg47Pro | missense_variant | 3/4 | ENST00000592588.7 | NP_001009.1 | |
RPS15 | NM_001308226.2 | c.161G>C | p.Arg54Pro | missense_variant | 3/4 | NP_001295155.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RPS15 | ENST00000592588.7 | c.140G>C | p.Arg47Pro | missense_variant | 3/4 | 1 | NM_001018.5 | ENSP00000467466.3 |
Frequencies
GnomAD3 genomes AF: 0.0000797 AC: 12AN: 150568Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0249 AC: 3087AN: 123918Hom.: 0 AF XY: 0.0234 AC XY: 1552AN XY: 66208
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.110 AC: 99241AN: 905186Hom.: 1 Cov.: 37 AF XY: 0.107 AC XY: 48472AN XY: 454910
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome AF: 0.0000797 AC: 12AN: 150568Hom.: 0 Cov.: 32 AF XY: 0.0000544 AC XY: 4AN XY: 73462
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 08, 2016 | - - |
RPS15-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 26, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;.;T;.;T;.;.;.;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;.;D;D;D;D;D;.;D;D;D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
.;.;H;.;.;.;.;.;.;.;.
PrimateAI
Pathogenic
D
REVEL
Benign
Sift4G
Benign
T;T;T;.;T;T;T;T;T;T;T
Polyphen
0.022
.;.;B;.;.;.;.;.;.;.;.
Vest4
MPC
1.9
ClinPred
T
GERP RS
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