8-56069824-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001146227.3(RPS20):c.343T>C(p.Ser115Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00578 in 1,495,880 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 79 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 99 hom. )

Consequence

RPS20
NM_001146227.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.347

Variant links:

Genes affected

RPS20 (HGNC:10405): (ribosomal protein S20) 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 S10P family of ribosomal proteins. It is located in the cytoplasm. This gene is co-transcribed with the small nucleolar RNA gene U54, which is located in its second intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Two transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Apr 2009]

RPS20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018868148).

BP6

Variant 8-56069824-A-G is Benign according to our data. Variant chr8-56069824-A-G is described in ClinVar as [Benign]. Clinvar id is 1232012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS20	NM_001146227.3 link	c.343T>C	p.Ser115Pro	missense_variant	Exon 5 of 6		NP_001139699.1	P60866-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
RPS20	ENST00000519807.5 link	c.343T>C	p.Ser115Pro	missense_variant	Exon 5 of 6	2	ENSP00000429374.1	P60866-2
RPS20	ENST00000618656.2 link	c.325T>C	p.Ser109Pro	missense_variant	Exon 4 of 5	3	ENSP00000478703.2	A0A7P0S5H5
RPS20	ENST00000676918.1 link	n.*3266T>C		non_coding_transcript_exon_variant	Exon 4 of 5		ENSP00000503327.1	P60866-1

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2955

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0602

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0179

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.00785

AC:

1209

AN:

153948

Hom.:

AF XY:

0.00747

AC XY:

610

AN XY:

81706

show subpopulations

Gnomad AFR exome

AF:

0.0699

Gnomad AMR exome

AF:

0.00652

Gnomad ASJ exome

AF:

0.00330

Gnomad EAS exome

AF:

0.0151

Gnomad SAS exome

AF:

0.00606

Gnomad FIN exome

AF:

0.0000656

Gnomad NFE exome

AF:

0.00233

Gnomad OTH exome

AF:

0.00600

GnomAD4 exome

AF:

0.00423

AC:

5681

AN:

1343644

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

2769

AN XY:

665856

show subpopulations

Gnomad4 AFR exome

AF:

0.0640

Gnomad4 AMR exome

AF:

0.00688

Gnomad4 ASJ exome

AF:

0.00375

Gnomad4 EAS exome

AF:

0.0226

Gnomad4 SAS exome

AF:

0.00573

Gnomad4 FIN exome

AF:

0.000102

Gnomad4 NFE exome

AF:

0.00161

Gnomad4 OTH exome

AF:

0.00740

GnomAD4 genome

AF:

0.0195

AC:

2964

AN:

152236

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

1429

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0604

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0179

Gnomad4 SAS

AF:

0.00601

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0118

Hom.:

Bravo

AF:

0.0221

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0665

AC:

ESP6500EA

AF:

0.00157

AC:

ExAC

AF:

0.0109

AC:

240

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2020

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial colorectal cancer type X

Benign:1

Jan 18, 2022

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.66

CADD

Benign

3.3

DANN

Benign

0.75

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.58

.;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.49

N;.

REVEL

Benign

0.037

Sift

Benign

0.14

T;.

Sift4G

Benign

0.14

T;T

Vest4

0.17

MPC

1.4

ClinPred

0.0030

GERP RS

0.81

gMVP

0.66

Splicing

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