19-49490262-G-A
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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
NM_012423.4 missense
Scores
3
4
11
Clinical Significance
Conservation
PhyloP100: 9.14
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 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 |
---|---|---|---|---|---|---|---|---|
RPL13A | NM_012423.4 | c.119G>A | p.Gly40Asp | missense_variant | 3/8 | ENST00000391857.9 | NP_036555.1 | |
RPL13A | NM_001270491.2 | c.-29-213G>A | intron_variant | NP_001257420.1 | ||||
RPL13A | NR_073024.2 | n.131G>A | non_coding_transcript_exon_variant | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RPL13A | ENST00000391857.9 | c.119G>A | p.Gly40Asp | missense_variant | 3/8 | 1 | NM_012423.4 | ENSP00000375730 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 152192Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000251 AC: 63AN: 251416Hom.: 0 AF XY: 0.000316 AC XY: 43AN XY: 135900
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GnomAD4 exome AF: 0.000220 AC: 322AN: 1461874Hom.: 0 Cov.: 32 AF XY: 0.000265 AC XY: 193AN XY: 727236
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GnomAD4 genome AF: 0.000243 AC: 37AN: 152310Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74470
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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 | Apr 17, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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