NM_001018.5:c.140G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

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. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 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

Publications

15 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 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 VariationId is 440242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

GnomAD2 exomes

AF:

0.0249

AC:

3087

AN:

123918

AF XY:

0.0234

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0523

AC:

1239

AN:

23690

American (AMR)

AF:

0.0551

AC:

1346

AN:

24418

Ashkenazi Jewish (ASJ)

AF:

0.0454

AC:

867

AN:

19106

East Asian (EAS)

AF:

0.0386

AC:

1335

AN:

34552

South Asian (SAS)

AF:

0.0461

AC:

2816

AN:

61098

European-Finnish (FIN)

AF:

0.0604

AC:

2442

AN:

40402

Middle Eastern (MID)

AF:

0.0626

AC:

214

AN:

3420

European-Non Finnish (NFE)

AF:

0.130

AC:

85606

AN:

656898

Other (OTH)

AF:

0.0811

AC:

3376

AN:

41602

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.252

Heterozygous variant carriers

13558

27116

40674

54232

67790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

4214

8428

12642

16856

21070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000797

AC:

AN:

150568

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73462

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000729

AC:

AN:

41136

American (AMR)

AF:

0.000133

AC:

AN:

15086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3442

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.00

AC:

AN:

4750

European-Finnish (FIN)

AF:

0.000288

AC:

AN:

10424

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000594

AC:

AN:

67336

Other (OTH)

AF:

0.00

AC:

AN:

2060

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.238

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

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;.;.;.;.;.;.;.;.

PhyloP100

9.3

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

Mutation Taster

=9/91

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over