10-78033793-A-T

Variant names:

• chr10-78033793-A-T
• rs3740254
• ENST00000435275.5:c.-109A>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The ENST00000435275.5(RPS24):​c.-109A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000594 in 1,346,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: RPS24 ENST00000435275.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000435275.5. 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.-109A>T		upstream_gene	N/A	NP_148982.1	P62847-2
	RPS24	NM_001142285.2		c.-109A>T		upstream_gene	N/A	NP_001135757.1	P62847-4
	RPS24	NM_001026.5		c.-109A>T		upstream_gene	N/A	NP_001017.1	P62847-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS24	ENST00000435275.5	TSL:2	c.-109A>T		5_prime_UTR	Exon 1 of 6	ENSP00000415549.1	E7ETK0
	RPS24	ENST00000613865.5	TSL:5	c.-109A>T		5_prime_UTR	Exon 1 of 5	ENSP00000478869.2	P62847-1
	RPS24	ENST00000913449.1		c.-109A>T		5_prime_UTR	Exon 1 of 6	ENSP00000583508.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000594 AC: 8 AN: 1346610 Hom.: 0 Cov.: 21 AF XY: 0.00000887 AC XY: 6 AN XY: 676060

African (AFR) AF: 0.00 AC: 0 AN: 31232

American (AMR) AF: 0.0000224 AC: 1 AN: 44558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25436

East Asian (EAS) AF: 0.00 AC: 0 AN: 39152

South Asian (SAS) AF: 0.0000595 AC: 5 AN: 84078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51716

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5566

European-Non Finnish (NFE) AF: 9.92e-7 AC: 1 AN: 1008172

Other (OTH) AF: 0.0000176 AC: 1 AN: 56700

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.94
PhyloP100		0.36
PromoterAI		-0.076	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3740254; hg19: chr10-79793551;