rs779783104

Variant names:

• chr10-78054612-G-C
• rs779783104
• NM_001142285.2:c.472G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-78054612-G-C
• chr10-78054612-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142285.2(RPS24):​c.472G>C​(p.Ala158Pro) variant causes a missense 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. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A158S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS24 NM_001142285.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• Publications: 0 publications found

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

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Diamond-Blackfan anemia 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09572703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS24	NM_001142285.2	c.472G>C	p.Ala158Pro	missense_variant	Exon 5 of 5		NP_001135757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS24	ENST00000440692.6	c.472G>C	p.Ala158Pro	missense_variant	Exon 5 of 5	3		ENSP00000414321.1
RPS24	ENST00000476545.6	n.*219G>C		non_coding_transcript_exon_variant	Exon 6 of 6	3		ENSP00000494169.1
RPS24	ENST00000476545.6	n.*219G>C		3_prime_UTR_variant	Exon 6 of 6	3		ENSP00000494169.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	11
DANN	Benign	0.95
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.17
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.089
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Vest4		0.32
MutPred		0.35		Loss of helix (P = 0.0304);
MVP		0.15
MPC		1.5
ClinPred		0.13	T
GERP RS		1.6
gMVP		0.069
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs779783104; hg19: chr10-79814370;