rs3738

Positions:

• chr5-82273474-A-C

Variant summary

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

The ENST00000296674.13(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 ENST00000296674.13 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS23	NM_001025.5	c.*2635T>G		3_prime_UTR_variant	4/4	ENST00000296674.13	NP_001016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS23	ENST00000296674.13	c.*2635T>G		3_prime_UTR_variant	4/4	1	NM_001025.5	ENSP00000296674	P1
RPS23	ENST00000651545.1	c.*2540T>G		3_prime_UTR_variant	5/5			ENSP00000498621	P1
ATG10	ENST00000508814.5	n.261-2671A>C		intron_variant, non_coding_transcript_variant		3
ATG10	ENST00000514253.2	n.192-2671A>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.0776

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.310

Alfa AF: 0.240 Hom.: 1298

Asia WGS AF: 0.129 AC: 447 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.7
DANN	Benign	0.76

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: rs3738; hg19: chr5-81569293;