dbSNP rs746098498: RPS24:p.Asn2Lys (chr10-78035354-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_033022.4(RPS24):c.6C>A(p.Asn2Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. N2N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

RPS24
NM_033022.4 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.203

Publications

0 publications found

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]

RPS24 Gene-Disease associations (from GenCC):

Diamond-Blackfan anemia 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
Diamond-Blackfan anemia
Inheritance: Unknown, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet

RPS24 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033022.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS24	NM_033022.4	MANE Select	c.6C>A	p.Asn2Lys	missense splice_region	Exon 2 of 6	NP_148982.1	P62847-2
RPS24	NM_001142285.2		c.6C>A	p.Asn2Lys	missense splice_region	Exon 2 of 5	NP_001135757.1	P62847-4
RPS24	NM_001026.5		c.6C>A	p.Asn2Lys	missense splice_region	Exon 2 of 5	NP_001017.1	P62847-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS24	ENST00000372360.9	TSL:1 MANE Select	c.6C>A	p.Asn2Lys	missense splice_region	Exon 2 of 6	ENSP00000361435.4	P62847-2
RPS24	ENST00000360830.9	TSL:1	c.6C>A	p.Asn2Lys	missense splice_region	Exon 2 of 7	ENSP00000354074.5	A0A2R8Y849
RPS24	ENST00000435275.5	TSL:2	c.6C>A	p.Asn2Lys	missense splice_region	Exon 2 of 6	ENSP00000415549.1	E7ETK0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.030

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

PhyloP100

-0.20

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.8

REVEL

Benign

0.11

Sift

Uncertain

0.0060

Sift4G

Benign

0.11

Polyphen

0.042

Vest4

0.67

MutPred

0.32

Loss of stability (P = 0.0486)

MVP

0.51

MPC

1.8

ClinPred

0.91

GERP RS

-0.14

PromoterAI

-0.050

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.64

Mutation Taster

=63/37

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.63

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.63

Position offset: 2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over