19-49490262-G-A

Variant summary

Our verdict is Likely benign. Variant got -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

3
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.14
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.39460102).
BS2
High AC in GnomAd4 at 37 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RPL13ANM_012423.4 linkuse as main transcriptc.119G>A p.Gly40Asp missense_variant 3/8 ENST00000391857.9 NP_036555.1
RPL13ANM_001270491.2 linkuse as main transcriptc.-29-213G>A intron_variant NP_001257420.1
RPL13ANR_073024.2 linkuse as main transcriptn.131G>A non_coding_transcript_exon_variant 3/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RPL13AENST00000391857.9 linkuse as main transcriptc.119G>A p.Gly40Asp missense_variant 3/81 NM_012423.4 ENSP00000375730 P1

Frequencies

GnomAD3 genomes
AF:
0.000237
AC:
36
AN:
152192
Hom.:
0
Cov.:
33
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
GnomAD3 exomes
AF:
0.000251
AC:
63
AN:
251416
Hom.:
0
AF XY:
0.000316
AC XY:
43
AN XY:
135900
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 SAS exome
AF:
0.000490
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.:
0
Cov.:
32
AF XY:
0.000265
AC XY:
193
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000243
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000246
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.000243
AC:
37
AN:
152310
Hom.:
0
Cov.:
33
AF XY:
0.000215
AC XY:
16
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000368
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000349
Hom.:
0
Bravo
AF:
0.000227
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000321
AC:
39
EpiCase
AF:
0.000164
EpiControl
AF:
0.000711

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 17, 2024The c.119G>A (p.G40D) alteration is located in exon 3 (coding exon 3) of the RPL13A gene. This alteration results from a G to A substitution at nucleotide position 119, causing the glycine (G) at amino acid position 40 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Pathogenic
0.32
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.23
T
Eigen
Benign
0.065
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.39
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.41
N
MutationTaster
Benign
1.0
D
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.29
Sift
Benign
0.49
T
Sift4G
Benign
0.53
T
Polyphen
0.048
B
Vest4
0.86
MVP
0.79
MPC
1.0
ClinPred
0.11
T
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.28
gMVP
0.85

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

LitVar

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

Other links and lift over

dbSNP: rs199838441; hg19: chr19-49993519; API