17-8377566-A-C
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2
The NM_000987.5(RPL26):āc.436T>Gā(p.Ter146GluextTer8) variant causes a stop lost change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000503 in 1,589,594 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.0000049 ( 0 hom. )
Consequence
RPL26
NM_000987.5 stop_lost
NM_000987.5 stop_lost
Scores
2
2
3
Clinical Significance
Conservation
PhyloP100: 9.17
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 -2 ACMG points.
PM4
?
Stoplost variant in NM_000987.5 Downstream stopcodon found after 42 codons.
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.436T>G | p.Ter146GluextTer8 | stop_lost | 4/4 | ENST00000648839.1 | |
RPL26 | NM_001315530.2 | c.436T>G | p.Ter146GluextTer8 | stop_lost | 4/4 | ||
RPL26 | NM_001315531.2 | c.436T>G | p.Ter146GluextTer8 | stop_lost | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL26 | ENST00000648839.1 | c.436T>G | p.Ter146GluextTer8 | stop_lost | 4/4 | NM_000987.5 | P1 | ||
ENST00000666354.1 | n.154-3479A>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000427 AC: 1AN: 234164Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 127520
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GnomAD4 exome AF: 0.00000487 AC: 7AN: 1437368Hom.: 0 Cov.: 29 AF XY: 0.00000280 AC XY: 2AN XY: 715276
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74390
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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. This variant has not been reported in the literature in individuals affected with RPL26-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change disrupts the translational stop signal of the RPL26 mRNA. It is expected to extend the length of the RPL26 protein by 8 additional amino acid residues. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
N;N;N;N
Vest4
0.19, 0.19, 0.40, 0.26
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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