19-49491441-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_012423.4(RPL13A):c.419G>A(p.Arg140His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 127,250 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000024 ( 0 hom., cov: 28)
Exomes 𝑓: 0.0000075 ( 1 hom. )
Failed GnomAD Quality Control
Consequence
RPL13A
NM_012423.4 missense
NM_012423.4 missense
Scores
4
6
5
Clinical Significance
Conservation
PhyloP100: 9.63
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
?
In a modified_residue Citrulline (size 0) in uniprot entity RL13A_HUMAN
PM2
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Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL13A | NM_012423.4 | c.419G>A | p.Arg140His | missense_variant | 7/8 | ENST00000391857.9 | |
RPL13A | NM_001270491.2 | c.236G>A | p.Arg79His | missense_variant | 6/7 | ||
RPL13A | NR_073024.2 | n.431G>A | non_coding_transcript_exon_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL13A | ENST00000391857.9 | c.419G>A | p.Arg140His | missense_variant | 7/8 | 1 | NM_012423.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000236 AC: 3AN: 127250Hom.: 0 Cov.: 28
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GnomAD3 exomes AF: 0.0000133 AC: 2AN: 150546Hom.: 0 AF XY: 0.0000244 AC XY: 2AN XY: 81980
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000746 AC: 8AN: 1072412Hom.: 1 Cov.: 29 AF XY: 0.0000113 AC XY: 6AN XY: 531428
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GnomAD4 genome ? AF: 0.0000236 AC: 3AN: 127250Hom.: 0 Cov.: 28 AF XY: 0.0000339 AC XY: 2AN XY: 59078
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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 submitter | clinical testing | Ambry Genetics | Nov 08, 2022 | The c.419G>A (p.R140H) alteration is located in exon 7 (coding exon 7) of the RPL13A gene. This alteration results from a G to A substitution at nucleotide position 419, causing the arginine (R) at amino acid position 140 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T
Polyphen
0.032
.;B
Vest4
MutPred
0.40
.;Loss of MoRF binding (P = 0.0114);
MVP
MPC
0.59
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at