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19-1440069-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001018.5(RPS15):c.140G>C(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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 32)
Exomes 𝑓: 0.11 ( 1 hom. )
Failed GnomAD Quality Control

Consequence

RPS15
NM_001018.5 missense

Scores

4
2
8

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 9.32
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 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 [Likely_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 GnomAd at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS15NM_001018.5 linkuse as main transcriptc.140G>C p.Arg47Pro missense_variant 3/4 ENST00000592588.7
RPS15NM_001308226.2 linkuse as main transcriptc.161G>C p.Arg54Pro missense_variant 3/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS15ENST00000592588.7 linkuse as main transcriptc.140G>C p.Arg47Pro missense_variant 3/41 NM_001018.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0000797
AC:
12
AN:
150568
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000729
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000133
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000288
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000594
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0249
AC:
3087
AN:
123918
Hom.:
0
AF XY:
0.0234
AC XY:
1552
AN XY:
66208
show subpopulations
Gnomad AFR exome
AF:
0.0172
Gnomad AMR exome
AF:
0.00449
Gnomad ASJ exome
AF:
0.00590
Gnomad EAS exome
AF:
0.0204
Gnomad SAS exome
AF:
0.00657
Gnomad FIN exome
AF:
0.103
Gnomad NFE exome
AF:
0.0306
Gnomad OTH exome
AF:
0.0111
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.110
AC:
99241
AN:
905186
Hom.:
1
Cov.:
37
AF XY:
0.107
AC XY:
48472
AN XY:
454910
show subpopulations
Gnomad4 AFR exome
AF:
0.0523
Gnomad4 AMR exome
AF:
0.0551
Gnomad4 ASJ exome
AF:
0.0454
Gnomad4 EAS exome
AF:
0.0386
Gnomad4 SAS exome
AF:
0.0461
Gnomad4 FIN exome
AF:
0.0604
Gnomad4 NFE exome
AF:
0.130
Gnomad4 OTH exome
AF:
0.0811
GnomAD4 genome
AF:
0.0000797
AC:
12
AN:
150568
Hom.:
0
Cov.:
32
AF XY:
0.0000544
AC XY:
4
AN XY:
73462
show subpopulations
Gnomad4 AFR
AF:
0.0000729
Gnomad4 AMR
AF:
0.000133
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000288
Gnomad4 NFE
AF:
0.0000594
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0240
Hom.:
0
ExAC
AF:
0.0363
AC:
3887

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesAug 08, 2016- -
RPS15-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 26, 2020This 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). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
Cadd
Uncertain
25
Dann
Benign
0.90
DEOGEN2
Benign
0.26
T;.;T;.;T;.;.;.;T;T;.
Eigen
Benign
-0.080
Eigen_PC
Benign
-0.11
FATHMM_MKL
Pathogenic
0.99
D
MetaRNN
Benign
0.0024
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.21
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.88
D
REVEL
Benign
0.26
Sift4G
Benign
0.081
T;T;T;.;T;T;T;T;T;T;T
Polyphen
0.022
.;.;B;.;.;.;.;.;.;.;.
Vest4
0.80
MPC
1.9
ClinPred
0.093
T
GERP RS
3.2
Varity_R
0.97
gMVP
0.99

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: rs201657403; hg19: chr19-1440068; COSMIC: COSV51830899; COSMIC: COSV51830899; API