5-82276365-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001025.5(RPS23):c.285+33C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,612,502 control chromosomes in the GnomAD database, including 275,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (21220 hom., cov: 32)
  • Exomes 𝑓: 0.58 (254187 hom.)
• Consequence: RPS23 NM_001025.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.55

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.987969E-7).
• BP6: Variant 5-82276365-G-C is Benign according to our data. Variant chr5-82276365-G-C is described in ClinVar as [Benign]. Clinvar id is 1327972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS23	NM_001025.5	c.285+33C>G		intron_variant		ENST00000296674.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS23	ENST00000296674.13	c.285+33C>G		intron_variant		1	NM_001025.5	P1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73832 AN: 151898 Hom.: 21198 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.509

GnomAD3 exomes AF: 0.607 AC: 150284 AN: 247446 Hom.: 48749 AF XY: 0.608 AC XY: 81538 AN XY: 134194

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.767

Gnomad ASJ exome AF: 0.512

Gnomad EAS exome AF: 0.905

Gnomad SAS exome AF: 0.659

Gnomad FIN exome AF: 0.583

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.588

GnomAD4 exome AF: 0.581 AC: 849007 AN: 1460486 Hom.: 254187 Cov.: 42 AF XY: 0.585 AC XY: 424702 AN XY: 726482

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.514

Gnomad4 EAS exome AF: 0.935

Gnomad4 SAS exome AF: 0.658

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.571

Gnomad4 OTH exome AF: 0.564

GnomAD4 genome AF: 0.486 AC: 73870 AN: 152016 Hom.: 21220 Cov.: 32 AF XY: 0.495 AC XY: 36775 AN XY: 74288

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.906

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.513

Alfa AF: 0.533 Hom.: 4259

Bravo AF: 0.477

TwinsUK AF: 0.576 AC: 2134

ALSPAC AF: 0.557 AC: 2145

ESP6500AA AF: 0.170 AC: 656

ESP6500EA AF: 0.571 AC: 4715

ExAC AF: 0.597 AC: 72102

Asia WGS AF: 0.753 AC: 2617 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Brachycephaly, trichomegaly, and developmental delay Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	0.14
Dann	Benign	0.65
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	9.0e-7	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P
PROVEAN	Benign	1.5	N
REVEL	Benign	0.025
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.33	T
Vest4		0.039
MutPred		0.41		Gain of glycosylation at P111 (P = 0.2225);
ClinPred		0.0051	T
GERP RS		-6.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs226200; hg19: chr5-81572184; COSMIC: COSV56994168; COSMIC: COSV56994168;