Genetic Variant NM_001146227.3:c.419G>C (chr8-56069748-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001146227.3(RPS20):c.419G>C(p.Cys140Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C140R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RPS20
NM_001146227.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0650

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Diamond-Blackfan anemia
Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Orphanet, Ambry Genetics
familial colorectal cancer
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
familial colorectal cancer type X
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Lynch syndrome
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

RPS20 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.064445585).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146227.3. 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
	RPS20	NM_001146227.3		c.419G>C	p.Cys140Ser	missense	Exon 5 of 6	NP_001139699.1	P60866-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS20	ENST00000519807.5	TSL:2	c.419G>C	p.Cys140Ser	missense	Exon 5 of 6	ENSP00000429374.1	P60866-2
RPS20	ENST00000618656.2	TSL:3	c.401G>C	p.Cys134Ser	missense	Exon 4 of 5	ENSP00000478703.2	A0A7P0S5H5
RPS20	ENST00000676918.1		n.*3342G>C		non_coding_transcript_exon	Exon 4 of 5	ENSP00000503327.1	P60866-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.0

(source)

DANN

Benign

0.61

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.31

M_CAP

Benign

0.0022

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

PhyloP100

-0.065

PrimateAI

Benign

0.36

PROVEAN

Benign

0.18

REVEL

Benign

0.023

Sift

Pathogenic

0.0

Vest4

0.20

MutPred

0.11

Gain of glycosylation at C140 (P = 0.0192)

MVP

0.043

MPC

1.5

ClinPred

0.071

GERP RS

1.0

gMVP

0.54

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over