17-8377641-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000987.5(RPL26):c.361C>T(p.Arg121Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,458,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
RPL26
NM_000987.5 missense
NM_000987.5 missense
Scores
2
5
7
Clinical Significance
Conservation
PhyloP100: 5.54
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 Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL26 | NM_000987.5 | c.361C>T | p.Arg121Trp | missense_variant | 4/4 | ENST00000648839.1 | |
RPL26 | NM_001315530.2 | c.361C>T | p.Arg121Trp | missense_variant | 4/4 | ||
RPL26 | NM_001315531.2 | c.361C>T | p.Arg121Trp | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL26 | ENST00000648839.1 | c.361C>T | p.Arg121Trp | missense_variant | 4/4 | NM_000987.5 | P1 | ||
ENST00000666354.1 | n.154-3404G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248430Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134584
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GnomAD4 exome AF: 0.00000480 AC: 7AN: 1458228Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 725620
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GnomAD4 genome ? Cov.: 33
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?
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33
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?
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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 | Feb 18, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). This variant has not been reported in the literature in individuals with RPL26-related conditions. This variant is present in population databases (rs763691423, ExAC 0.006%). This sequence change replaces arginine with tryptophan at codon 121 of the RPL26 protein (p.Arg121Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
DEOGEN2
Uncertain
D;D;D;D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
Polyphen
B;B;B;B;B
Vest4
0.59, 0.60, 0.56
MutPred
Gain of catalytic residue at L119 (P = 0.0081);Gain of catalytic residue at L119 (P = 0.0081);Gain of catalytic residue at L119 (P = 0.0081);Gain of catalytic residue at L119 (P = 0.0081);Gain of catalytic residue at L119 (P = 0.0081);
MVP
0.47
MPC
1.0
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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