10-78034119-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033022.4(RPS24):c.3+215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 625,242 control chromosomes in the GnomAD database, including 1,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.059 (835 hom., cov: 30)
  • Exomes 𝑓: 0.0081 (280 hom.)
• Consequence: RPS24 NM_033022.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0640

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-78034119-C-T is Benign according to our data. Variant chr10-78034119-C-T is described in ClinVar as [Benign]. Clinvar id is 1260481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS24	NM_033022.4	c.3+215C>T		intron_variant		ENST00000372360.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS24	ENST00000372360.9	c.3+215C>T		intron_variant		1	NM_033022.4	P4

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 8781 AN: 150420 Hom.: 830 Cov.: 30

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0256

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.0435

GnomAD4 exome AF: 0.00806 AC: 3825 AN: 474722 Hom.: 280 Cov.: 5 AF XY: 0.00650 AC XY: 1652 AN XY: 254344

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.0155

Gnomad4 ASJ exome AF: 0.00317

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000495

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.000908

Gnomad4 OTH exome AF: 0.0186

GnomAD4 genome AF: 0.0586 AC: 8814 AN: 150520 Hom.: 835 Cov.: 30 AF XY: 0.0566 AC XY: 4148 AN XY: 73344

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.0330

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00113

Gnomad4 OTH AF: 0.0431

Alfa AF: 0.0324 Hom.: 43

Bravo AF: 0.0652

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.9
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs7071081; hg19: chr10-79793877;