10-78040201-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000435275.5(RPS24):c.391C>A(p.Gln131Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,613,192 control chromosomes in the GnomAD database, including 1,931 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/15 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 1012 hom., cov: 33)

Exomes 𝑓: 0.0074 ( 919 hom. )

Consequence

RPS24
ENST00000435275.5 missense, splice_region

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.64

Publications

12 publications found

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]

RPS24 Gene-Disease associations (from GenCC):

Diamond-Blackfan anemia
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
Diamond-Blackfan anemia 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

RPS24 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013203025).

BP6

Variant 10-78040201-C-A is Benign according to our data. Variant chr10-78040201-C-A is described in ClinVar as Benign. ClinVar VariationId is 301097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RPS24	NM_033022.4	MANE Select	c.391-3C>A	splice_region intron	N/A	NP_148982.1
RPS24	NM_001142285.2		c.390+2897C>A	intron	N/A	NP_001135757.1
RPS24	NM_001026.5		c.391-414C>A	intron	N/A	NP_001017.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RPS24	ENST00000435275.5	TSL:2	c.391C>A	p.Gln131Lys	missense splice_region	Exon 5 of 6	ENSP00000415549.1
RPS24	ENST00000372360.9	TSL:1 MANE Select	c.391-3C>A		splice_region intron	N/A	ENSP00000361435.4
RPS24	ENST00000360830.9	TSL:1	c.394-3C>A		splice_region intron	N/A	ENSP00000354074.5

Frequencies

GnomAD3 genomes

AF:

0.0629

AC:

9573

AN:

152126

Hom.:

1012

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.0154

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.0497

GnomAD2 exomes

AF:

0.0174

AC:

4365

AN:

251212

AF XY:

0.0131

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.0114

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.0110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000854

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.00741

AC:

10826

AN:

1460948

Hom.:

919

Cov.:

AF XY:

0.00652

AC XY:

4741

AN XY:

726896

show subpopulations

African (AFR)

AF:

0.223

AC:

7409

AN:

33278

American (AMR)

AF:

0.0127

AC:

567

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00130

AC:

AN:

26124

East Asian (EAS)

AF:

0.0227

AC:

900

AN:

39680

South Asian (SAS)

AF:

0.00174

AC:

150

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.0205

AC:

118

AN:

5764

European-Non Finnish (NFE)

AF:

0.000666

AC:

740

AN:

1111400

Other (OTH)

AF:

0.0150

AC:

908

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

424

848

1271

1695

2119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0630

AC:

9590

AN:

152244

Hom.:

1012

Cov.:

AF XY:

0.0606

AC XY:

4509

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.216

AC:

8964

AN:

41486

American (AMR)

AF:

0.0239

AC:

366

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.0154

AC:

AN:

5192

South Asian (SAS)

AF:

0.00207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68034

Other (OTH)

AF:

0.0501

AC:

106

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

379

759

1138

1518

1897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0242

Hom.:

1229

Bravo

AF:

0.0726

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.214

AC:

945

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.0216

AC:

2622

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.00124

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Diamond-Blackfan anemia (2)

Diamond-Blackfan anemia 3 (2)

not provided (1)

not specified (1)

RPS24-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.66

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.0

PhyloP100

1.6

PROVEAN

Benign

1.4

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.18

ClinPred

0.0069

GERP RS

4.1

Mutation Taster

=53/47

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over