5-82276365-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

1
14

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.55
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
RPS23NM_001025.5 linkc.285+33C>G intron_variant Intron 3 of 3 ENST00000296674.13 NP_001016.1 P62266A8K517

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPS23ENST00000296674.13 linkc.285+33C>G intron_variant Intron 3 of 3 1 NM_001025.5 ENSP00000296674.8 P62266

Frequencies

GnomAD3 genomes
AF:
0.486
AC:
73832
AN:
151898
Hom.:
21198
Cov.:
32
show subpopulations
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
GnomAD2 exomes
AF:
0.607
AC:
150284
AN:
247446
AF XY:
0.608
show subpopulations
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 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
show subpopulations
Gnomad4 AFR exome
AF:
0.156
AC:
5227
AN:
33476
Gnomad4 AMR exome
AF:
0.750
AC:
33456
AN:
44586
Gnomad4 ASJ exome
AF:
0.514
AC:
13435
AN:
26124
Gnomad4 EAS exome
AF:
0.935
AC:
37103
AN:
39690
Gnomad4 SAS exome
AF:
0.658
AC:
56744
AN:
86206
Gnomad4 FIN exome
AF:
0.587
AC:
31327
AN:
53350
Gnomad4 NFE exome
AF:
0.571
AC:
634684
AN:
1110958
Gnomad4 Remaining exome
AF:
0.564
AC:
34008
AN:
60338
Heterozygous variant carriers
0
18374
36748
55123
73497
91871
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
17576
35152
52728
70304
87880
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.486
AC:
73870
AN:
152016
Hom.:
21220
Cov.:
32
AF XY:
0.495
AC XY:
36775
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.174
AC:
0.174249
AN:
0.174249
Gnomad4 AMR
AF:
0.648
AC:
0.647602
AN:
0.647602
Gnomad4 ASJ
AF:
0.520
AC:
0.520185
AN:
0.520185
Gnomad4 EAS
AF:
0.906
AC:
0.906455
AN:
0.906455
Gnomad4 SAS
AF:
0.675
AC:
0.674969
AN:
0.674969
Gnomad4 FIN
AF:
0.590
AC:
0.589763
AN:
0.589763
Gnomad4 NFE
AF:
0.577
AC:
0.576664
AN:
0.576664
Gnomad4 OTH
AF:
0.513
AC:
0.513258
AN:
0.513258
Heterozygous variant carriers
0
1641
3282
4924
6565
8206
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
648
1296
1944
2592
3240
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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
LINK: link

Submissions by phenotype

Brachycephaly, trichomegaly, and developmental delay Benign:1
Nov 07, 2021
Genome-Nilou Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

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
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
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

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