11-75404831-C-G

Variant names:

• chr11-75404831-C-G
• rs73006114
• NM_001005.5:c.698C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005.5(RPS3):​c.698C>G​(p.Pro233Arg) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS3 NM_001005.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13

Genes affected

RPS3 (HGNC:10420): (ribosomal protein S3) 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, where it forms part of the domain where translation is initiated. The protein belongs to the S3P family of ribosomal proteins. Studies of the mouse and rat proteins have demonstrated that the protein has an extraribosomal role as an endonuclease involved in the repair of UV-induced DNA damage. The protein appears to be located in both the cytoplasm and nucleus but not in the nucleolus. Higher levels of expression of this gene in colon adenocarcinomas and adenomatous polyps compared to adjacent normal colonic mucosa have been observed. This gene is co-transcribed with the small nucleolar RNA genes U15A and U15B, which are located in its first and fifth introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11278954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS3	NM_001005.5	c.698C>G	p.Pro233Arg	missense_variant	Exon 6 of 7	ENST00000531188.6	NP_000996.2
RPS3	NM_001260506.2	c.746C>G	p.Pro249Arg	missense_variant	Exon 6 of 7		NP_001247435.1
RPS3	NM_001256802.2	c.698C>G	p.Pro233Arg	missense_variant	Exon 6 of 7		NP_001243731.1
RPS3	NM_001260507.2	c.320C>G	p.Pro107Arg	missense_variant	Exon 5 of 6		NP_001247436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS3	ENST00000531188.6	c.698C>G	p.Pro233Arg	missense_variant	Exon 6 of 7	1	NM_001005.5	ENSP00000434643.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T;.;T;T;T;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.72	.;T;T;.;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	L;.;.;L;.;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.48	N;N;N;N;N;N
REVEL	Benign	0.085
Sift	Uncertain	0.024	D;D;D;D;D;D
Sift4G	Benign	0.15	T;T;T;T;T;T
Polyphen		0.16	B;.;.;B;.;B
Vest4		0.33
MutPred		0.17		Loss of glycosylation at P233 (P = 0.0112);.;.;Loss of glycosylation at P233 (P = 0.0112);.;Loss of glycosylation at P233 (P = 0.0112);
MVP		0.24
MPC		1.4
ClinPred		0.079	T
GERP RS		0.81
Varity_R		0.13
gMVP		0.23

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: rs73006114; hg19: chr11-75115875;