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GeneBe

8-144791802-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001317782.2(RPL8):c.251C>G(p.Thr84Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RPL8
NM_001317782.2 missense

Scores

7
6
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.29
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL8NM_001317782.2 linkuse as main transcriptc.251C>G p.Thr84Arg missense_variant 2/5 ENST00000528957.6
RPL8NM_000973.5 linkuse as main transcriptc.251C>G p.Thr84Arg missense_variant 3/6
RPL8NM_001317771.2 linkuse as main transcriptc.251C>G p.Thr84Arg missense_variant 3/6
RPL8NM_033301.3 linkuse as main transcriptc.251C>G p.Thr84Arg missense_variant 3/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL8ENST00000528957.6 linkuse as main transcriptc.251C>G p.Thr84Arg missense_variant 2/51 NM_001317782.2 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
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 submitterclinical testingAmbry GeneticsJul 12, 2023The c.251C>G (p.T84R) alteration is located in exon 3 (coding exon 2) of the RPL8 gene. This alteration results from a C to G substitution at nucleotide position 251, causing the threonine (T) at amino acid position 84 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.85
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
Cadd
Pathogenic
28
Dann
Uncertain
0.98
DEOGEN2
Benign
0.27
T;T;T;.;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Pathogenic
1.0
D
M_CAP
Benign
0.019
T
MetaRNN
Pathogenic
0.75
D;D;D;D;D
MetaSVM
Benign
-0.28
T
MutationAssessor
Pathogenic
3.9
H;H;H;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Pathogenic
-5.3
D;D;D;D;D
REVEL
Uncertain
0.42
Sift
Pathogenic
0.0
D;D;D;D;D
Sift4G
Benign
0.065
T;T;T;.;T
Polyphen
0.36
B;B;B;.;.
Vest4
0.78
MutPred
0.58
Gain of MoRF binding (P = 0.1167);Gain of MoRF binding (P = 0.1167);Gain of MoRF binding (P = 0.1167);Gain of MoRF binding (P = 0.1167);Gain of MoRF binding (P = 0.1167);
MVP
0.64
MPC
1.9
ClinPred
1.0
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.89
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-146017187; API