17-8377614-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000987.5(RPL26):c.388A>G(p.Lys130Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000311 in 1,607,670 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
RPL26
NM_000987.5 missense
NM_000987.5 missense
Scores
1
2
11
Clinical Significance
Conservation
PhyloP100: 6.05
Genes affected
RPL26 (HGNC:10327): (ribosomal protein L26) 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 L24P family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Mutations in this gene result in Diamond-Blackfan anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.16609165).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL26 | NM_000987.5 | c.388A>G | p.Lys130Glu | missense_variant | 4/4 | ENST00000648839.1 | |
RPL26 | NM_001315530.2 | c.388A>G | p.Lys130Glu | missense_variant | 4/4 | ||
RPL26 | NM_001315531.2 | c.388A>G | p.Lys130Glu | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL26 | ENST00000648839.1 | c.388A>G | p.Lys130Glu | missense_variant | 4/4 | NM_000987.5 | P1 | ||
ENST00000666354.1 | n.154-3431T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152252Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000815 AC: 2AN: 245362Hom.: 0 AF XY: 0.00000751 AC XY: 1AN XY: 133182
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1455300Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3AN XY: 724264
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152370Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74512
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Diamond-Blackfan anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 15, 2023 | This variant is present in population databases (rs150329538, gnomAD 0.007%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. This variant has not been reported in the literature in individuals affected with RPL26-related conditions. This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 130 of the RPL26 protein (p.Lys130Glu). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
DEOGEN2
Benign
T;T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
T
Polyphen
B;B;B;B;B
Vest4
0.51, 0.49, 0.51
MVP
0.63
MPC
1.3
ClinPred
T
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