chr8-144791997-C-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS2
The NM_001317782.2(RPL8):c.133G>A(p.Val45Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,456,296 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: 0.0000034 ( 0 hom. )
Consequence
RPL8
NM_001317782.2 missense
NM_001317782.2 missense
Scores
2
3
13
Clinical Significance
Conservation
PhyloP100: 6.61
Genes affected
RPL8 (HGNC:10368): (ribosomal protein L8) 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 L2P family of ribosomal proteins. It is located in the cytoplasm. In rat, the protein associates with the 5.8S rRNA, very likely participates in the binding of aminoacyl-tRNA, and is a constituent of the elongation factor 2-binding site at the ribosomal subunit interface. Alternatively spliced transcript variants encoding the same protein exist. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]
MIR6850 (HGNC:50093): (microRNA 6850) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BS2
?
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL8 | NM_001317782.2 | c.133G>A | p.Val45Ile | missense_variant | 1/5 | ENST00000528957.6 | |
MIR6850 | NR_106909.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL8 | ENST00000528957.6 | c.133G>A | p.Val45Ile | missense_variant | 1/5 | 1 | NM_001317782.2 | P1 | |
MIR6850 | ENST00000612162.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1456296Hom.: 0 Cov.: 33 AF XY: 0.00000414 AC XY: 3AN XY: 723918
GnomAD4 exome
AF:
AC:
5
AN:
1456296
Hom.:
Cov.:
33
AF XY:
AC XY:
3
AN XY:
723918
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
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 | Sep 27, 2021 | The c.133G>A (p.V45I) alteration is located in exon 2 (coding exon 1) of the RPL8 gene. This alteration results from a G to A substitution at nucleotide position 133, causing the valine (V) at amino acid position 45 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;.;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;L;.;.
MutationTaster
Benign
D;D;D;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;.;T
Polyphen
B;.;B;B;.;.
Vest4
MutPred
Gain of ubiquitination at K46 (P = 0.0898);Gain of ubiquitination at K46 (P = 0.0898);Gain of ubiquitination at K46 (P = 0.0898);Gain of ubiquitination at K46 (P = 0.0898);Gain of ubiquitination at K46 (P = 0.0898);Gain of ubiquitination at K46 (P = 0.0898);
MVP
MPC
0.84
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.