dbSNP rs752461630: RPS15:p.Gln41Pro (chr19-1440051-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001018.5(RPS15):c.122A>C(p.Gln41Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000385 in 1,558,274 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

RPS15
NM_001018.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.75

Publications

0 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 Gene-Disease associations (from GenCC):

Diamond-Blackfan anemia
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

RPS15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS15	NM_001018.5	MANE Select	c.122A>C	p.Gln41Pro	missense	Exon 3 of 4	NP_001009.1	P62841
	RPS15	NM_001308226.2		c.143A>C	p.Gln48Pro	missense	Exon 3 of 4	NP_001295155.1	K7ELC2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS15	ENST00000592588.7	TSL:1 MANE Select	c.122A>C	p.Gln41Pro	missense	Exon 3 of 4	ENSP00000467466.3	P62841
RPS15	ENST00000592623.5	TSL:1	c.41A>C	p.Gln14Pro	missense	Exon 2 of 3	ENSP00000474433.2	A0A0B4J2B4
RPS15	ENST00000593052.5	TSL:2	c.143A>C	p.Gln48Pro	missense	Exon 3 of 4	ENSP00000466010.1	K7ELC2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000127

AC:

AN:

158074

AF XY:

0.0000118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000805

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000356

AC:

AN:

1406016

Hom.:

Cov.:

AF XY:

0.00000432

AC XY:

AN XY:

694116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32356

American (AMR)

AF:

0.000111

AC:

AN:

36018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25194

East Asian (EAS)

AF:

0.00

AC:

AN:

37090

South Asian (SAS)

AF:

0.00

AC:

AN:

79872

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4550

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1084076

Other (OTH)

AF:

0.0000172

AC:

AN:

58278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41476

American (AMR)

AF:

0.0000654

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.30

CADD

Uncertain

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.033

Eigen

Benign

-0.099

Eigen_PC

Benign

-0.017

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.81

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.1

PhyloP100

8.8

PrimateAI

Pathogenic

0.83

REVEL

Uncertain

0.35

Sift4G

Benign

0.19

Polyphen

0.0010

Vest4

0.90

MutPred

0.39

Gain of glycosylation at Q41 (P = 0.0052)

MVP

0.94

MPC

1.6

ClinPred

0.43

GERP RS

4.3

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

4.1

Varity_R

0.88

gMVP

0.99

Mutation Taster

=35/65

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over