19-48615400-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000979.4(RPL18):​c.539G>A​(p.Arg180Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,578 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: 0.0000021 ( 0 hom. )

Consequence

RPL18
NM_000979.4 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.14
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RPL18NM_000979.4 linkc.539G>A p.Arg180Gln missense_variant 7/7 ENST00000549920.6 NP_000970.1 Q07020-1A0A024QZD1
RPL18NM_001270490.2 linkc.452G>A p.Arg151Gln missense_variant 6/6 NP_001257419.1 Q07020-2
RPL18NR_073022.2 linkn.566G>A non_coding_transcript_exon_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RPL18ENST00000549920.6 linkc.539G>A p.Arg180Gln missense_variant 7/71 NM_000979.4 ENSP00000447001.1 Q07020-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250994
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135676
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
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:
0.00000205
AC:
3
AN:
1460578
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726430
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2

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 testingLabcorp Genetics (formerly Invitae), LabcorpApr 09, 2022This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 180 of the RPL18 protein (p.Arg180Gln). This variant is present in population databases (rs758912189, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RPL18-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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
0.95
BayesDel_addAF
Uncertain
0.073
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.55
D;T;.;T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.87
D;D;D;D
M_CAP
Benign
0.014
T
MetaRNN
Uncertain
0.56
D;D;D;D
MetaSVM
Benign
-0.43
T
MutationAssessor
Uncertain
2.4
M;.;.;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-3.1
D;D;D;D
REVEL
Benign
0.26
Sift
Benign
0.036
D;D;D;D
Sift4G
Benign
0.064
T;T;T;T
Polyphen
0.40
B;.;.;.
Vest4
0.74
MutPred
0.59
Loss of methylation at R180 (P = 0.0092);.;.;.;
MVP
0.56
MPC
0.91
ClinPred
0.77
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.39
gMVP
0.49

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: rs758912189; hg19: chr19-49118657; API