rs863223400

Variant names:

• chr8-56073724-C-CT
• rs863223400
• NM_001023.4:c.147dupA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001023.4(RPS20):​c.147dupA​(p.Val50SerfsTer23) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS20 NM_001023.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 0.299

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]

SNORD54 (HGNC:10204): (small nucleolar RNA, C/D box 54)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS20	NM_001023.4	c.147dupA	p.Val50SerfsTer23	frameshift_variant	Exon 3 of 4	ENST00000009589.8	NP_001014.1
RPS20	NM_001146227.3	c.147dupA	p.Val50SerfsTer23	frameshift_variant	Exon 3 of 6		NP_001139699.1
SNORD54	NR_002437.1	n.*114dupA		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS20	ENST00000009589.8	c.147dupA	p.Val50SerfsTer23	frameshift_variant	Exon 3 of 4	1	NM_001023.4	ENSP00000009589.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:2

Sep 01, 2014

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Jul 05, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val50Serfs*23) in the RPS20 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 70 amino acid(s) of the RPS20 protein. This premature translational stop signal has been observed in individual(s) with colorectal cancer (PMID: 24941021). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 208850). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects RPS20 function (PMID: 24941021). -

not specified Uncertain:1

Feb 04, 2020

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.147dupA variant, located in coding exon 3 of the RPS20 gene, results from a duplication of A at nucleotide position 147, causing a translational frameshift with a predicted alternate stop codon. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of RPS20 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs863223400; hg19: chr8-56986283;