NM_033022.4:c.-36T>G

Variant names:

• chr10-78033866-T-G
• rs45533232
• NM_033022.4:c.-36T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_033022.4(RPS24):​c.-36T>G variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0011 in 1,613,844 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (5 hom.)
• Consequence: RPS24 NM_033022.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.01
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 10-78033866-T-G is Benign according to our data. Variant chr10-78033866-T-G is described in ClinVar as Benign. ClinVar VariationId is 301090.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 91 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.-36T>G		5_prime_UTR	Exon 1 of 6	NP_148982.1	P62847-2
	RPS24	NM_001142285.2		c.-36T>G		5_prime_UTR	Exon 1 of 5	NP_001135757.1	P62847-4
	RPS24	NM_001026.5		c.-36T>G		5_prime_UTR	Exon 1 of 5	NP_001017.1	P62847-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS24	ENST00000372360.9	TSL:1 MANE Select	c.-36T>G		5_prime_UTR	Exon 1 of 6	ENSP00000361435.4	P62847-2
	RPS24	ENST00000360830.9	TSL:1	c.-36T>G		5_prime_UTR	Exon 1 of 7	ENSP00000354074.5	A0A2R8Y849
	RPS24	ENST00000435275.5	TSL:2	c.-36T>G		5_prime_UTR	Exon 1 of 6	ENSP00000415549.1	E7ETK0

Frequencies

GnomAD3 genomes AF: 0.000598 AC: 91 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000820 AC: 206 AN: 251362 AF XY: 0.000839

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000491

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000325

Gnomad NFE exome AF: 0.00153

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00115 AC: 1684 AN: 1461502 Hom.: 5 Cov.: 30 AF XY: 0.00110 AC XY: 802 AN XY: 727082

African (AFR) AF: 0.000119 AC: 4 AN: 33476

American (AMR) AF: 0.000447 AC: 20 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.000601 AC: 32 AN: 53276

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

European-Non Finnish (NFE) AF: 0.00143 AC: 1585 AN: 1111804

Other (OTH) AF: 0.000696 AC: 42 AN: 60376

GnomAD4 genome AF: 0.000597 AC: 91 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.000510 AC XY: 38 AN XY: 74498

African (AFR) AF: 0.000264 AC: 11 AN: 41588

American (AMR) AF: 0.000196 AC: 3 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00109 AC: 74 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000646 Hom.: 0

Bravo AF: 0.000582

ClinVar

ClinVar submissions

Significance: 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	-0.40
CADD	Benign	18
DANN	Benign	0.77
PhyloP100		4.0
PromoterAI		0.15	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Mutation Taster		=257/43	polymorphism

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: rs45533232; hg19: chr10-79793624;