5-82276027-G-C

Variant names:

• chr5-82276027-G-C
• rs226201
• NM_001025.5:c.*82C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001025.5(RPS23):​c.*82C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000855 in 1,169,632 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: RPS23 NM_001025.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS23	NM_001025.5	c.*82C>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000296674.13	NP_001016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS23	ENST00000296674.13	c.*82C>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_001025.5	ENSP00000296674.8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.55e-7 AC: 1 AN: 1169632 Hom.: 0 Cov.: 15 AF XY: 0.00000171 AC XY: 1 AN XY: 585430

African (AFR) AF: 0.00 AC: 0 AN: 26072

American (AMR) AF: 0.00 AC: 0 AN: 29940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19844

East Asian (EAS) AF: 0.00 AC: 0 AN: 38112

South Asian (SAS) AF: 0.0000149 AC: 1 AN: 67034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3332

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 885338

Other (OTH) AF: 0.00 AC: 0 AN: 49806

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.98
DANN	Benign	0.62
PhyloP100		0.11
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

Other links and lift over

dbSNP: rs226201; hg19: chr5-81571846;