10-78033904-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_033022.4(RPS24):​c.3G>A​(p.Met1?) variant causes a start lost, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RPS24
NM_033022.4 start_lost, splice_region

Scores

5
8
3
Splicing: ADA: 0.9998
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04
Variant links:
Genes affected
RPS24 (HGNC:10411): (ribosomal protein S24) 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 S24E family of ribosomal proteins. It is located in the cytoplasm. Multiple transcript variants encoding different isoforms have been found for this gene. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Mutations in this gene result in Diamond-Blackfan anemia. [provided by RefSeq, Nov 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPS24NM_033022.4 linkc.3G>A p.Met1? start_lost, splice_region_variant Exon 1 of 6 ENST00000372360.9 NP_148982.1 P62847-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPS24ENST00000372360.9 linkc.3G>A p.Met1? start_lost, splice_region_variant Exon 1 of 6 1 NM_033022.4 ENSP00000361435.4 P62847-2
RPS24ENST00000435275.5 linkc.3G>A p.Met1? start_lost, splice_region_variant Exon 1 of 6 2 ENSP00000415549.1 E7ETK0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Diamond-Blackfan anemia 3 Uncertain:1
May 20, 2021
Genetics and Molecular Pathology, SA Pathology
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.62
D
BayesDel_noAF
Pathogenic
0.38
CADD
Pathogenic
38
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.54
.;.;D;.;.;.;.;.
Eigen
Pathogenic
0.75
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.90
.;D;D;.;D;D;D;D
M_CAP
Pathogenic
0.35
D
MetaRNN
Pathogenic
0.98
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.26
T
PROVEAN
Benign
-2.0
.;N;.;.;.;N;N;N
REVEL
Uncertain
0.63
Sift
Uncertain
0.0080
.;D;.;.;.;D;D;D
Sift4G
Benign
0.080
.;T;T;.;.;T;T;D
Polyphen
0.087, 0.26, 0.91
.;B;B;.;P;.;.;.
Vest4
0.93, 0.93, 0.95, 0.72
MutPred
1.0
Loss of disorder (P = 0.0638);Loss of disorder (P = 0.0638);Loss of disorder (P = 0.0638);Loss of disorder (P = 0.0638);Loss of disorder (P = 0.0638);Loss of disorder (P = 0.0638);Loss of disorder (P = 0.0638);Loss of disorder (P = 0.0638);
MVP
0.84
ClinPred
1.0
D
GERP RS
5.2
RBP_binding_hub_radar
1.0
RBP_regulation_power_radar
3.8
Varity_R
0.75
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.98
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-79793662; API