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GeneBe

19-1440087-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001018.5(RPS15):c.158A>C(p.Gln53Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000127 in 1,580,456 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RPS15
NM_001018.5 missense

Scores

2
3
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.96
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.18059802).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS15NM_001018.5 linkuse as main transcriptc.158A>C p.Gln53Pro missense_variant 3/4 ENST00000592588.7
RPS15NM_001308226.2 linkuse as main transcriptc.179A>C p.Gln60Pro missense_variant 3/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS15ENST00000592588.7 linkuse as main transcriptc.158A>C p.Gln53Pro missense_variant 3/41 NM_001018.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152248
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000214
AC:
4
AN:
187276
Hom.:
0
AF XY:
0.0000198
AC XY:
2
AN XY:
100960
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000493
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000112
AC:
16
AN:
1428208
Hom.:
0
Cov.:
33
AF XY:
0.00000849
AC XY:
6
AN XY:
706880
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000137
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152248
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000378

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 18, 2023The c.158A>C (p.Q53P) alteration is located in exon 3 (coding exon 3) of the RPS15 gene. This alteration results from a A to C substitution at nucleotide position 158, causing the glutamine (Q) at amino acid position 53 to be replaced by a proline (P). 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
Benign
0.23
BayesDel_addAF
Uncertain
0.049
T
BayesDel_noAF
Uncertain
-0.020
Cadd
Benign
21
Dann
Benign
0.78
DEOGEN2
Benign
0.0020
T;.;T;.;T;.;.;.;T;T;.
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.31
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Benign
0.0088
T
MetaRNN
Benign
0.18
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.83
D
REVEL
Uncertain
0.33
Sift4G
Benign
0.52
T;T;T;.;T;T;T;T;T;T;T
Polyphen
0.0
.;.;B;.;.;.;.;.;.;.;.
Vest4
0.70
MutPred
0.48
.;.;Gain of glycosylation at Q53 (P = 0.0272);.;.;.;Gain of glycosylation at Q53 (P = 0.0272);.;.;Gain of glycosylation at Q53 (P = 0.0272);.;
MVP
0.80
MPC
1.6
ClinPred
0.13
T
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.76
gMVP
0.98

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1281286559; hg19: chr19-1440086; API