chr10-78033793-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000613865.5(RPS24):​c.-109A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 1,498,660 control chromosomes in the GnomAD database, including 2,891 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 343 hom., cov: 32)
Exomes 𝑓: 0.041 ( 2548 hom. )

Consequence

RPS24
ENST00000613865.5 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.363
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 10-78033793-A-G is Benign according to our data. Variant chr10-78033793-A-G is described in ClinVar as [Benign]. Clinvar id is 301088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS24ENST00000435275.5 linkuse as main transcriptc.-109A>G 5_prime_UTR_variant 1/62 A1
RPS24ENST00000613865.5 linkuse as main transcriptc.-109A>G 5_prime_UTR_variant 1/55 A1P62847-1
RPS24ENST00000645440.1 linkuse as main transcript upstream_gene_variant A1

Frequencies

GnomAD3 genomes
AF:
0.0457
AC:
6948
AN:
152110
Hom.:
343
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0303
Gnomad AMI
AF:
0.0384
Gnomad AMR
AF:
0.0959
Gnomad ASJ
AF:
0.0113
Gnomad EAS
AF:
0.236
Gnomad SAS
AF:
0.156
Gnomad FIN
AF:
0.0314
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.0256
Gnomad OTH
AF:
0.0458
GnomAD4 exome
AF:
0.0415
AC:
55864
AN:
1346432
Hom.:
2548
Cov.:
21
AF XY:
0.0438
AC XY:
29627
AN XY:
675988
show subpopulations
Gnomad4 AFR exome
AF:
0.0298
Gnomad4 AMR exome
AF:
0.0961
Gnomad4 ASJ exome
AF:
0.0106
Gnomad4 EAS exome
AF:
0.215
Gnomad4 SAS exome
AF:
0.135
Gnomad4 FIN exome
AF:
0.0345
Gnomad4 NFE exome
AF:
0.0257
Gnomad4 OTH exome
AF:
0.0505
GnomAD4 genome
AF:
0.0457
AC:
6961
AN:
152228
Hom.:
343
Cov.:
32
AF XY:
0.0503
AC XY:
3741
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.0303
Gnomad4 AMR
AF:
0.0963
Gnomad4 ASJ
AF:
0.0113
Gnomad4 EAS
AF:
0.236
Gnomad4 SAS
AF:
0.156
Gnomad4 FIN
AF:
0.0314
Gnomad4 NFE
AF:
0.0256
Gnomad4 OTH
AF:
0.0506
Alfa
AF:
0.0123
Hom.:
4
Bravo
AF:
0.0469
Asia WGS
AF:
0.197
AC:
686
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

POLR3-related leukodystrophy Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Diamond-Blackfan anemia 3 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Diamond-Blackfan anemia Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
CADD
Benign
15
DANN
Benign
0.79

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3740254; hg19: chr10-79793551; COSMIC: COSV62602305; COSMIC: COSV62602305; API