10-78033879-C-T

Variant names:

• chr10-78033879-C-T
• rs766457744
• NM_033022.4:c.-23C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_033022.4(RPS24):​c.-23C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: RPS24 NM_033022.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.542
• 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, Unknown Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Diamond-Blackfan anemia 3

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 10-78033879-C-T is Benign according to our data. Variant chr10-78033879-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 877454.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 11 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS24	NM_033022.4	MANE Select	c.-23C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_148982.1	P62847-2
	RPS24	NM_033022.4	MANE Select	c.-23C>T		5_prime_UTR	Exon 1 of 6	NP_148982.1	P62847-2
	RPS24	NM_001142285.2		c.-23C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001135757.1	P62847-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS24	ENST00000372360.9	TSL:1 MANE Select	c.-23C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000361435.4	P62847-2
	RPS24	ENST00000360830.9	TSL:1	c.-23C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000354074.5	A0A2R8Y849
	RPS24	ENST00000435275.5	TSL:2	c.-23C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000415549.1	E7ETK0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251398 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461696 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727174

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111930

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Diamond-Blackfan anemia 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		0.54
PromoterAI		-0.12	Neutral

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

Other links and lift over

dbSNP: rs766457744; hg19: chr10-79793637;