5-82275850-C-T

Variant names:

• chr5-82275850-C-T
• rs226202
• NM_001025.5:c.*259G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001025.5(RPS23):​c.*259G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 436,024 control chromosomes in the GnomAD database, including 111,536 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 0.70 (37519 hom., cov: 32)
  • Exomes 𝑓: 0.72 (74017 hom.)
• Consequence: RPS23 NM_001025.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.61
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS23	NM_001025.5	MANE Select	c.*259G>A		3_prime_UTR	Exon 4 of 4	NP_001016.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS23	ENST00000296674.13	TSL:1 MANE Select	c.*259G>A		3_prime_UTR	Exon 4 of 4	ENSP00000296674.8
	RPS23	ENST00000651545.1		c.*259G>A		3_prime_UTR	Exon 4 of 5	ENSP00000498621.1
	RPS23	ENST00000510019.5	TSL:4	c.*259G>A		3_prime_UTR	Exon 4 of 4	ENSP00000425833.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106275 AN: 151950 Hom.: 37461 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.700

GnomAD4 exome AF: 0.717 AC: 203536 AN: 283956 Hom.: 74017 Cov.: 2 AF XY: 0.717 AC XY: 105349 AN XY: 146924

African (AFR) AF: 0.640 AC: 5345 AN: 8350

American (AMR) AF: 0.796 AC: 7901 AN: 9930

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 6019 AN: 9562

East Asian (EAS) AF: 0.950 AC: 19863 AN: 20902

South Asian (SAS) AF: 0.738 AC: 12586 AN: 17052

European-Finnish (FIN) AF: 0.681 AC: 14743 AN: 21642

Middle Eastern (MID) AF: 0.674 AC: 905 AN: 1342

European-Non Finnish (NFE) AF: 0.697 AC: 123863 AN: 177608

Other (OTH) AF: 0.701 AC: 12311 AN: 17568

GnomAD4 genome AF: 0.700 AC: 106391 AN: 152068 Hom.: 37519 Cov.: 32 AF XY: 0.702 AC XY: 52181 AN XY: 74328

African (AFR) AF: 0.648 AC: 26830 AN: 41424

American (AMR) AF: 0.775 AC: 11851 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2213 AN: 3472

East Asian (EAS) AF: 0.912 AC: 4721 AN: 5178

South Asian (SAS) AF: 0.772 AC: 3726 AN: 4826

European-Finnish (FIN) AF: 0.681 AC: 7193 AN: 10562

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47684 AN: 68002

Other (OTH) AF: 0.703 AC: 1484 AN: 2110

Alfa AF: 0.704 Hom.: 148177

Bravo AF: 0.704

Asia WGS AF: 0.824 AC: 2866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.25
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs226202; hg19: chr5-81571669;