19-49490262-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_012423.4(RPL13A):c.119G>A(p.Gly40Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,614,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

RPL13A
NM_012423.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.14

Publications

2 publications found

Variant links:

Genes affected

RPL13A (HGNC:10304): (ribosomal protein L13a) 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 L13P family of ribosomal proteins that is a component of the 60S subunit. The encoded protein also plays a role in the repression of inflammatory genes as a component of the IFN-gamma-activated inhibitor of translation (GAIT) complex. This gene is co-transcribed with the small nucleolar RNA genes U32, U33, U34, and U35, which are located in the second, fourth, fifth, and sixth introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

RPL13A links:

SNORD32A (HGNC:10159): (small nucleolar RNA, C/D box 32A) Predicted to act upstream of or within glucose metabolic process; insulin secretion; and reactive oxygen species metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

SNORD32A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.39460102).

BS2

High AC in GnomAd4 at 37 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012423.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL13A	NM_012423.4	MANE Select	c.119G>A	p.Gly40Asp	missense	Exon 3 of 8	NP_036555.1	P40429
RPL13A	NM_001270491.2		c.-29-213G>A		intron	N/A	NP_001257420.1	Q8J015
RPL13A	NR_073024.2		n.131G>A		non_coding_transcript_exon	Exon 3 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL13A	ENST00000391857.9	TSL:1 MANE Select	c.119G>A	p.Gly40Asp	missense	Exon 3 of 8	ENSP00000375730.4	P40429
RPL13A	ENST00000624069.3	TSL:1	n.109G>A		non_coding_transcript_exon	Exon 3 of 8	ENSP00000485546.1	A0A096LPE0
RPL13A	ENST00000467825.2	TSL:5	c.113G>A	p.Gly38Asp	missense	Exon 3 of 8	ENSP00000470037.2	M0QYS1

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000251

AC:

AN:

251416

AF XY:

0.000316

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000220

AC:

322

AN:

1461874

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

193

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33480

American (AMR)

AF:

0.000157

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000243

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000246

AC:

273

AN:

1112006

Other (OTH)

AF:

0.000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000243

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41568

American (AMR)

AF:

0.000458

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00104

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000356

Hom.:

Bravo

AF:

0.000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000321

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000711

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.32

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Benign

0.065

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.019

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.41

PhyloP100

9.1

PROVEAN

Benign

-1.8

REVEL

Benign

0.29

Sift

Benign

0.49

Sift4G

Benign

0.53

Polyphen

0.048

Vest4

0.86

MVP

0.79

MPC

1.0

ClinPred

0.11

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.85

Mutation Taster

=23/77

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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