chr16-89561665-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP2BP4_StrongBA1

The NM_000977.4(RPL13):c.334G>A(p.Ala112Thr) variant causes a missense change. The variant allele was found at a frequency of 0.19 in 1,613,752 control chromosomes in the GnomAD database, including 32,280 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2354 hom., cov: 33)

Exomes 𝑓: 0.19 ( 29926 hom. )

Consequence

RPL13
NM_000977.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.82

Publications

31 publications found

Variant links:

Genes affected

RPL13 (HGNC:10303): (ribosomal protein L13) 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 60S subunit. The protein belongs to the L13E family of ribosomal proteins. It is located in the cytoplasm. This gene is expressed at significantly higher levels in benign breast lesions than in breast carcinomas. Alternatively spliced transcript variants encoding distinct 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. [provided by RefSeq, Jul 2011]

RPL13 links:

SNORD68 (HGNC:32729): (small nucleolar RNA, C/D box 68)

SNORD68 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 5 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: -0.32157 (below the threshold of 3.09). Trascript score misZ: -0.64596 (below the threshold of 3.09). GenCC associations: The gene is linked to spondyloepimetaphyseal dysplasia, Isidor-Toutain type, spondyloepiphyseal dysplasia.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022824407).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000977.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL13	NM_000977.4	MANE Select	c.334G>A	p.Ala112Thr	missense	Exon 4 of 6	NP_000968.2
RPL13	NM_033251.2		c.334G>A	p.Ala112Thr	missense	Exon 3 of 5	NP_150254.1	P26373-1
RPL13	NM_001243131.1		c.267+67G>A		intron	N/A	NP_001230060.1	P26373-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL13	ENST00000311528.10	TSL:1 MANE Select	c.334G>A	p.Ala112Thr	missense	Exon 4 of 6	ENSP00000307889.5	P26373-1
RPL13	ENST00000393099.4	TSL:1	c.334G>A	p.Ala112Thr	missense	Exon 3 of 5	ENSP00000376811.3	P26373-1
RPL13	ENST00000562879.5	TSL:1	n.174G>A		non_coding_transcript_exon	Exon 3 of 5	ENSP00000457174.1	H3BTH3

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23435

AN:

152110

Hom.:

2353

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0405

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0911

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.212

GnomAD2 exomes

AF:

0.163

AC:

40893

AN:

250942

AF XY:

0.167

show subpopulations

Gnomad AFR exome

AF:

0.0372

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.000816

Gnomad FIN exome

AF:

0.173

Gnomad NFE exome

AF:

0.226

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.194

AC:

283638

AN:

1461524

Hom.:

29926

Cov.:

AF XY:

0.193

AC XY:

140637

AN XY:

727040

show subpopulations

African (AFR)

AF:

0.0360

AC:

1206

AN:

33480

American (AMR)

AF:

0.134

AC:

5983

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

5363

AN:

26136

East Asian (EAS)

AF:

0.000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.102

AC:

8758

AN:

86258

European-Finnish (FIN)

AF:

0.182

AC:

9644

AN:

53112

Middle Eastern (MID)

AF:

0.306

AC:

1764

AN:

5758

European-Non Finnish (NFE)

AF:

0.216

AC:

239811

AN:

1111984

Other (OTH)

AF:

0.184

AC:

11089

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

13846

27692

41539

55385

69231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7816

15632

23448

31264

39080

<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:

0.154

AC:

23426

AN:

152228

Hom.:

2354

Cov.:

AF XY:

0.149

AC XY:

11100

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0404

AC:

1680

AN:

41562

American (AMR)

AF:

0.190

AC:

2906

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

669

AN:

3470

East Asian (EAS)

AF:

0.00154

AC:

AN:

5186

South Asian (SAS)

AF:

0.0916

AC:

442

AN:

4824

European-Finnish (FIN)

AF:

0.171

AC:

1809

AN:

10572

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.223

AC:

15185

AN:

68004

Other (OTH)

AF:

0.209

AC:

442

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

976

1951

2927

3902

4878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<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:

0.191

Hom.:

2199

Bravo

AF:

0.152

TwinsUK

AF:

0.199

AC:

739

ALSPAC

AF:

0.210

AC:

809

ESP6500AA

AF:

0.0494

AC:

217

ESP6500EA

AF:

0.210

AC:

1810

ExAC

AF:

0.161

AC:

19594

EpiCase

AF:

0.238

EpiControl

AF:

0.236

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

Eigen

Benign

-0.024

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

6.8

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.81

REVEL

Benign

0.069

Sift

Benign

0.24

Sift4G

Benign

0.30

Polyphen

0.0030

Vest4

0.21

MPC

0.26

ClinPred

0.024

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.16

gMVP

0.53

Mutation Taster

=86/14

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

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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