Genetic Variant RPS11:p.Val111Val (chr19-49498026-A-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001015.5(RPS11):c.333A>T(p.Val111Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,612,732 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 21 hom. )

Consequence

RPS11
NM_001015.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.824

Publications

2 publications found

Variant links:

Genes affected

RPS11 (HGNC:10384): (ribosomal protein S11) 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 member of the S17P family of ribosomal proteins that is a component of the 40S subunit. This gene is co-transcribed with the small nucleolar RNA gene U35B, which is located in the third intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. [provided by RefSeq, Jul 2012]

RPS11 links:

SNORD35B (HGNC:17365): (small nucleolar RNA, C/D box 35B)

SNORD35B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.00798586).

BP6

Variant 19-49498026-A-T is Benign according to our data. Variant chr19-49498026-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2650249.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 180 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001015.5. 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
	RPS11	NM_001015.5	MANE Select	c.333A>T	p.Val111Val	synonymous	Exon 4 of 5	NP_001006.1	P62280
	SNORD35B	NR_001285.1		n.*220A>T		downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS11	ENST00000270625.7	TSL:1 MANE Select	c.333A>T	p.Val111Val	synonymous	Exon 4 of 5	ENSP00000270625.1	P62280
RPS11	ENST00000599561.1	TSL:5	c.229A>T	p.Thr77Ser	missense	Exon 4 of 5	ENSP00000471874.1	M0R1H6
RPS11	ENST00000596873.1	TSL:2	c.333A>T	p.Val111Val	synonymous	Exon 4 of 4	ENSP00000470447.1	M0QZC5

Frequencies

GnomAD3 genomes

AF:

0.00119

AC:

181

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000787

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00828

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00219

AC:

550

AN:

251376

AF XY:

0.00272

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00153

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00175

AC:

2557

AN:

1460556

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

1503

AN XY:

726598

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33438

American (AMR)

AF:

0.000693

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0101

AC:

871

AN:

86198

European-Finnish (FIN)

AF:

0.000131

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00632

AC:

AN:

4744

European-Non Finnish (NFE)

AF:

0.00129

AC:

1430

AN:

1111988

Other (OTH)

AF:

0.00197

AC:

119

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

155

309

464

618

773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.00118

AC:

180

AN:

152176

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41508

American (AMR)

AF:

0.000786

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00808

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00160

AC:

109

AN:

68002

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00122

Hom.:

Bravo

AF:

0.000956

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00241

AC:

292

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00261

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.8

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.030

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0080

PhyloP100

0.82

Sift4G

Benign

0.19

Vest4

0.20

MVP

0.65

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=90/10

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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