rs746098498

Variant names:

• chr10-78035354-C-A
• NM_033022.4:c.6C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-78035354-C-A
• chr10-78035354-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPS24 NM_033022.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS24	NM_033022.4	c.6C>A	p.Asn2Lys	missense_variant, splice_region_variant	Exon 2 of 6	ENST00000372360.9	NP_148982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS24	ENST00000372360.9	c.6C>A	p.Asn2Lys	missense_variant, splice_region_variant	Exon 2 of 6	1	NM_033022.4	ENSP00000361435.4
RPS24	ENST00000435275.5	c.6C>A	p.Asn2Lys	missense_variant, splice_region_variant	Exon 2 of 6	2		ENSP00000415549.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;.;T;.;.;.;.;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.97	.;D;D;.;D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.39	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L;.;L;.;L;.;L;L
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.8	.;N;.;.;.;N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0060	.;D;.;.;.;D;D;D
Sift4G	Benign	0.11	.;T;T;.;.;T;T;D
Polyphen		0.042, 0.10	.;B;B;.;B;.;.;.
Vest4		0.67, 0.66, 0.67, 0.62
MutPred		0.32		Loss of stability (P = 0.0486);Loss of stability (P = 0.0486);Loss of stability (P = 0.0486);Loss of stability (P = 0.0486);Loss of stability (P = 0.0486);Loss of stability (P = 0.0486);Loss of stability (P = 0.0486);Loss of stability (P = 0.0486);
MVP		0.51
MPC		1.8
ClinPred		0.91	D
GERP RS		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.49
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-79795112;