8-56073117-C-A

Position:

• chr8-56073117-C-A

Variant summary

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

The NM_001023.4(RPS20):​c.333G>T​(p.Glu111Asp) variant causes a missense 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 (★). Synonymous variant affecting the same amino acid position (i.e. E111E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS20 NM_001023.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.93

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]

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/exons	MANE	UniProt
RPS20	NM_001023.4	c.333G>T	p.Glu111Asp	missense_variant	4/4	ENST00000009589.8
RPS20	NM_001146227.3	c.333G>T	p.Glu111Asp	missense_variant, splice_region_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS20	ENST00000009589.8	c.333G>T	p.Glu111Asp	missense_variant	4/4	1	NM_001023.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Oct 15, 2023

This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 111 of the RPS20 protein (p.Glu111Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RPS20-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	.;.;T;.;T;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.42	.;T;.;.;D;D
M_CAP	Benign	0.0085	T
MetaRNN	Uncertain	0.54	D;D;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;N;.;N;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.9	N;.;N;N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.24	T;.;T;T;T;T
Sift4G	Benign	0.56	T;T;T;T;T;T
Polyphen		0.0080	.;.;B;.;B;.
Vest4		0.62
MutPred		0.60		Loss of disorder (P = 0.1784);Loss of disorder (P = 0.1784);Loss of disorder (P = 0.1784);.;Loss of disorder (P = 0.1784);.;
MVP		0.92
MPC		1.1
ClinPred		0.69	D
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.54
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-56985676;