rs3738

Variant names:

• chr5-82273474-A-C
• rs3738
• NM_001025.5:c.*2635T>G

Variant summary

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

The NM_001025.5(RPS23):​c.*2635T>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 0.321 in 148,594 control chromosomes in the GnomAD database, including 9,960 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 0.32 (9960 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: RPS23 NM_001025.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 29 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS23	NM_001025.5	MANE Select	c.*2635T>G		3_prime_UTR	Exon 4 of 4	NP_001016.1	P62266

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS23	ENST00000296674.13	TSL:1 MANE Select	c.*2635T>G		3_prime_UTR	Exon 4 of 4	ENSP00000296674.8	P62266
	RPS23	ENST00000651545.1		c.*2540T>G		3_prime_UTR	Exon 5 of 5	ENSP00000498621.1	P62266
	ATG10	ENST00000866604.1		c.*5-2671A>C		intron	N/A	ENSP00000536663.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 47692 AN: 148474 Hom.: 9958 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.321 AC: 47694 AN: 148586 Hom.: 9960 Cov.: 32 AF XY: 0.316 AC XY: 22990 AN XY: 72658

African (AFR) AF: 0.435 AC: 16646 AN: 38234

American (AMR) AF: 0.231 AC: 3514 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1303 AN: 3430

East Asian (EAS) AF: 0.0776 AC: 403 AN: 5190

South Asian (SAS) AF: 0.165 AC: 792 AN: 4802

European-Finnish (FIN) AF: 0.320 AC: 3373 AN: 10542

Middle Eastern (MID) AF: 0.369 AC: 107 AN: 290

European-Non Finnish (NFE) AF: 0.301 AC: 20471 AN: 67912

Other (OTH) AF: 0.310 AC: 643 AN: 2072

Alfa AF: 0.240 Hom.: 1298

Asia WGS AF: 0.129 AC: 447 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.7
DANN	Benign	0.76
PhyloP100		0.16
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: rs3738; hg19: chr5-81569293;