Menu
GeneBe

19-48615425-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_000979.4(RPL18):c.514C>T(p.Arg172Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R172R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

RPL18
NM_000979.4 missense

Scores

9
9
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.93
Variant links:
Genes affected
RPL18 (HGNC:10310): (ribosomal protein L18) 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 member of the L18E family of ribosomal proteins that is a component of the 60S subunit. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.818

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL18NM_000979.4 linkuse as main transcriptc.514C>T p.Arg172Trp missense_variant 7/7 ENST00000549920.6
RPL18NM_001270490.2 linkuse as main transcriptc.427C>T p.Arg143Trp missense_variant 6/6
RPL18NR_073022.2 linkuse as main transcriptn.541C>T non_coding_transcript_exon_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL18ENST00000549920.6 linkuse as main transcriptc.514C>T p.Arg172Trp missense_variant 7/71 NM_000979.4 P1Q07020-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152194
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250546
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135534
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1460818
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726546
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152312
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeAug 11, 2023This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 172 of the RPL18 protein (p.Arg172Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RPL18-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Uncertain
0.13
Cadd
Pathogenic
29
Dann
Pathogenic
1.0
DEOGEN2
Uncertain
0.64
D;T;.;T
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.89
D;D;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.82
D;D;D;D
MetaSVM
Uncertain
0.27
D
MutationAssessor
Uncertain
2.9
M;.;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.91
D
PROVEAN
Pathogenic
-6.8
D;D;D;D
REVEL
Uncertain
0.60
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
D;.;.;.
Vest4
0.77
MVP
0.43
MPC
0.79
ClinPred
0.99
D
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.80
gMVP
0.59

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

LitVar

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

Other links and lift over

dbSNP: rs199925096; hg19: chr19-49118682; API