rs226201

Positions:

• chr5-82276027-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001025.5(RPS23):​c.*82C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,319,230 control chromosomes in the GnomAD database, including 221,972 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (20487 hom., cov: 31)
  • Exomes 𝑓: 0.58 (201485 hom.)
• Consequence: RPS23 NM_001025.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107

Genes affected

RPS23 (HGNC:10410): (ribosomal protein S23) 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 S12P family of ribosomal proteins. It is located in the cytoplasm. The protein shares significant amino acid similarity with S. cerevisiae ribosomal protein S28. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ATG10 (HGNC:20315): (autophagy related 10) Autophagy is a process for the bulk degradation of cytosolic compartments by lysosomes. ATG10 is an E2-like enzyme involved in 2 ubiquitin-like modifications essential for autophagosome formation: ATG12 (MIM 609608)-ATG5 (MIM 604261) conjugation and modification of a soluble form of MAP-LC3 (MAP1LC3A; MIM 601242), a homolog of yeast Apg8, to a membrane-bound form (Nemoto et al., 2003 [PubMed 12890687]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS23	NM_001025.5	c.*82C>T		3_prime_UTR_variant	4/4	ENST00000296674.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS23	ENST00000296674.13	c.*82C>T		3_prime_UTR_variant	4/4	1	NM_001025.5	P1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72043 AN: 151846 Hom.: 20464 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.578 AC: 675202 AN: 1167266 Hom.: 201485 Cov.: 15 AF XY: 0.582 AC XY: 339824 AN XY: 584234

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.729

Gnomad4 ASJ exome AF: 0.472

Gnomad4 EAS exome AF: 0.936

Gnomad4 SAS exome AF: 0.651

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.569

Gnomad4 OTH exome AF: 0.556

GnomAD4 genome AF: 0.474 AC: 72077 AN: 151964 Hom.: 20487 Cov.: 31 AF XY: 0.483 AC XY: 35902 AN XY: 74274

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.908

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.499

Alfa AF: 0.552 Hom.: 7435

Bravo AF: 0.465

Asia WGS AF: 0.750 AC: 2607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs226201; hg19: chr5-81571846;