17-8377625-C-G
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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):āc.377G>Cā(p.Arg126Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000435 in 1,608,944 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R126H) has been classified as Uncertain significance.
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.0000041 ( 0 hom. )
Consequence
RPL26
NM_000987.5 missense
NM_000987.5 missense
Scores
3
7
4
Clinical Significance
Conservation
PhyloP100: 6.06
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 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL26 | NM_000987.5 | c.377G>C | p.Arg126Pro | missense_variant | 4/4 | ENST00000648839.1 | |
RPL26 | NM_001315530.2 | c.377G>C | p.Arg126Pro | missense_variant | 4/4 | ||
RPL26 | NM_001315531.2 | c.377G>C | p.Arg126Pro | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL26 | ENST00000648839.1 | c.377G>C | p.Arg126Pro | missense_variant | 4/4 | NM_000987.5 | P1 | ||
ENST00000666354.1 | n.154-3420C>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152134Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000412 AC: 6AN: 1456810Hom.: 0 Cov.: 30 AF XY: 0.00000552 AC XY: 4AN XY: 724982
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152134Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74310
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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 | Sep 17, 2022 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest 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 variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 126 of the RPL26 protein (p.Arg126Pro). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
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
P;P;P;P;P
Vest4
0.53, 0.53, 0.51, 0.53
MutPred
Loss of MoRF binding (P = 0.0515);Loss of MoRF binding (P = 0.0515);Loss of MoRF binding (P = 0.0515);Loss of MoRF binding (P = 0.0515);Loss of MoRF binding (P = 0.0515);
MVP
0.48
MPC
1.6
ClinPred
D
GERP RS
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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