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GeneBe

19-48615413-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000979.4(RPL18):c.526C>T(p.Arg176Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,612,998 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RPL18
NM_000979.4 missense

Scores

7
6
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54
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 Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL18NM_000979.4 linkuse as main transcriptc.526C>T p.Arg176Cys missense_variant 7/7 ENST00000549920.6
RPL18NM_001270490.2 linkuse as main transcriptc.439C>T p.Arg147Cys missense_variant 6/6
RPL18NR_073022.2 linkuse as main transcriptn.553C>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.526C>T p.Arg176Cys missense_variant 7/71 NM_000979.4 P1Q07020-1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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:
0.0000319
AC:
8
AN:
250874
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135624
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1460770
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
726558
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.0000896
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152228
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000330
AC:
4

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 testingInvitaeJun 04, 2023In 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. 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. This variant has not been reported in the literature in individuals affected with RPL18-related conditions. This variant is present in population databases (rs780751812, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 176 of the RPL18 protein (p.Arg176Cys). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.40
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Pathogenic
0.32
Cadd
Pathogenic
28
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.54
D;T;.;T
Eigen
Benign
0.18
Eigen_PC
Benign
0.21
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Benign
0.037
D
MetaRNN
Uncertain
0.70
D;D;D;D
MetaSVM
Benign
-0.36
T
MutationAssessor
Pathogenic
3.0
M;.;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.89
D
PROVEAN
Pathogenic
-6.3
D;D;D;D
REVEL
Benign
0.26
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Uncertain
0.057
T;T;T;T
Polyphen
0.22
B;.;.;.
Vest4
0.77
MVP
0.61
MPC
1.0
ClinPred
0.86
D
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.67
gMVP
0.52

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: rs780751812; hg19: chr19-49118670; API