19-1440069-G-C

Variant names:

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 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

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]

RPS15 links:

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 [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 rank	MANE	Protein	UniProt
RPS15	NM_001018.5 link	c.140G>C	p.Arg47Pro	missense_variant	Exon 3 of 4	ENST00000592588.7	NP_001009.1	P62841
RPS15	NM_001308226.2 link	c.161G>C	p.Arg54Pro	missense_variant	Exon 3 of 4		NP_001295155.1	K7ELC2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS15	ENST00000592588.7 link	c.140G>C	p.Arg47Pro	missense_variant	Exon 3 of 4	1	NM_001018.5	ENSP00000467466.3		P62841

Frequencies

GnomAD3 genomes

AF:

0.0000797

AC:

AN:

150568

Hom.:

Cov.:

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.:

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.:

Cov.:

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:

AN:

150568

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

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.:

ExAC

AF:

0.0363

AC:

3887

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Aug 08, 2016

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

RPS15-related disorder

Benign:1

Oct 26, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

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

LIST_S2

Benign

0.86

.;.;D;D;D;D;D;.;D;D;D

MetaRNN

Benign

0.0024

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Pathogenic

3.8

.;.;H;.;.;.;.;.;.;.;.

PrimateAI

Pathogenic

0.88

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over