19-1440080-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000592588.7(RPS15):​c.151C>G​(p.Arg51Gly) variant causes a missense 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. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RPS15
ENST00000592588.7 missense

Scores

2
2
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.312
Variant links:
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17955834).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RPS15NM_001018.5 linkuse as main transcriptc.151C>G p.Arg51Gly missense_variant 3/4 ENST00000592588.7 NP_001009.1
RPS15NM_001308226.2 linkuse as main transcriptc.172C>G p.Arg58Gly missense_variant 3/4 NP_001295155.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RPS15ENST00000592588.7 linkuse as main transcriptc.151C>G p.Arg51Gly missense_variant 3/41 NM_001018.5 ENSP00000467466 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 16, 2024The c.151C>G (p.R51G) alteration is located in exon 3 (coding exon 3) of the RPS15 gene. This alteration results from a C to G substitution at nucleotide position 151, causing the arginine (R) at amino acid position 51 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.85
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
16
DANN
Benign
0.91
DEOGEN2
Benign
0.11
T;.;T;.;T;.;.;.;T;T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.49
N
LIST_S2
Uncertain
0.87
.;.;D;D;D;D;D;.;D;D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.18
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.6
.;.;M;.;.;.;.;.;.;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.85
D
REVEL
Benign
0.19
Sift4G
Benign
0.12
T;T;T;.;T;T;T;T;T;T;T
Polyphen
0.038
.;.;B;.;.;.;.;.;.;.;.
Vest4
0.60
MutPred
0.46
.;.;Loss of methylation at R51 (P = 0.0261);.;.;.;Loss of methylation at R51 (P = 0.0261);.;.;Loss of methylation at R51 (P = 0.0261);.;
MVP
0.58
MPC
1.7
ClinPred
0.43
T
GERP RS
-8.5
Varity_R
0.72
gMVP
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1440079; API