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GeneBe

8-144792039-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001317782.2(RPL8):c.91G>C(p.Ala31Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000594 in 1,608,912 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00062 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00059 ( 2 hom. )

Consequence

RPL8
NM_001317782.2 missense

Scores

1
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76
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]
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.057048082).
BS2
High AC in GnomAd at 95 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL8NM_001317782.2 linkuse as main transcriptc.91G>C p.Ala31Pro missense_variant 1/5 ENST00000528957.6
MIR6850NR_106909.1 linkuse as main transcript upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL8ENST00000528957.6 linkuse as main transcriptc.91G>C p.Ala31Pro missense_variant 1/51 NM_001317782.2 P1
MIR6850ENST00000612162.1 linkuse as main transcript upstream_gene_variant

Frequencies

GnomAD3 genomes
AF:
0.000624
AC:
95
AN:
152238
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000282
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00121
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000655
AC:
157
AN:
239734
Hom.:
0
AF XY:
0.000625
AC XY:
82
AN XY:
131176
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000297
Gnomad ASJ exome
AF:
0.000206
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000831
Gnomad NFE exome
AF:
0.00113
Gnomad OTH exome
AF:
0.00119
GnomAD4 exome
AF:
0.000590
AC:
860
AN:
1456556
Hom.:
2
Cov.:
33
AF XY:
0.000620
AC XY:
449
AN XY:
724460
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000363
Gnomad4 ASJ exome
AF:
0.0000770
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000935
Gnomad4 NFE exome
AF:
0.000684
Gnomad4 OTH exome
AF:
0.000565
GnomAD4 genome
AF:
0.000624
AC:
95
AN:
152356
Hom.:
1
Cov.:
33
AF XY:
0.000483
AC XY:
36
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000282
Gnomad4 NFE
AF:
0.00121
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000777
Hom.:
0
Bravo
AF:
0.000552
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.00130
AC:
5
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000584
AC:
5
ExAC
AF:
0.000702
AC:
85
EpiCase
AF:
0.00120
EpiControl
AF:
0.000830

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 GeneticsJan 18, 2022The c.91G>C (p.A31P) alteration is located in exon 2 (coding exon 1) of the RPL8 gene. This alteration results from a G to C substitution at nucleotide position 91, causing the alanine (A) at amino acid position 31 to be replaced by a proline (P). 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
Benign
0.11
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.24
Cadd
Uncertain
24
Dann
Uncertain
0.99
DEOGEN2
Benign
0.031
T;T;T;T;.;T
Eigen
Benign
-0.20
Eigen_PC
Benign
0.025
FATHMM_MKL
Uncertain
0.90
D
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.057
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.32
N;.;N;N;.;.
MutationTaster
Benign
1.0
D;D;D;N
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-0.28
N;N;N;N;N;N
REVEL
Benign
0.10
Sift
Benign
0.54
T;T;T;T;T;T
Sift4G
Benign
0.38
T;T;T;T;.;T
Polyphen
0.0
B;.;B;B;.;.
Vest4
0.73
MVP
0.66
MPC
1.1
ClinPred
0.098
T
GERP RS
5.0
Varity_R
0.31
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11539895; hg19: chr8-146017424; COSMIC: COSV99068721; COSMIC: COSV99068721; API