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GeneBe

19-48615920-G-A

Variant summary

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

The NM_000979.4(RPL18):c.448C>T(p.Arg150Trp) 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 1,613,656 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R150Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

RPL18
NM_000979.4 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL18NM_000979.4 linkuse as main transcriptc.448C>T p.Arg150Trp missense_variant 6/7 ENST00000549920.6
RPL18NM_001270490.2 linkuse as main transcriptc.361C>T p.Arg121Trp missense_variant 5/6
RPL18NR_073022.2 linkuse as main transcriptn.475C>T non_coding_transcript_exon_variant 6/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL18ENST00000549920.6 linkuse as main transcriptc.448C>T p.Arg150Trp missense_variant 6/71 NM_000979.4 P1Q07020-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
249826
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135198
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.0000655
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461494
Hom.:
0
Cov.:
32
AF XY:
0.0000110
AC XY:
8
AN XY:
727010
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000247
AC:
3
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

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 GeneticsMay 31, 2022The c.448C>T (p.R150W) alteration is located in exon 6 (coding exon 6) of the RPL18 gene. This alteration results from a C to T substitution at nucleotide position 448, causing the arginine (R) at amino acid position 150 to be replaced by a tryptophan (W). 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
0.95
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Pathogenic
0.22
Cadd
Pathogenic
26
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.54
D;.;T;T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.25
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.87
D;D;D;D
M_CAP
Benign
0.037
D
MetaRNN
Uncertain
0.70
D;D;D;D
MetaSVM
Benign
-0.64
T
MutationAssessor
Benign
2.0
M;.;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-5.9
D;D;D;D
REVEL
Uncertain
0.63
Sift
Benign
0.053
T;D;T;D
Sift4G
Uncertain
0.041
D;D;D;D
Polyphen
0.028
B;.;.;.
Vest4
0.85
MutPred
0.69
Loss of disorder (P = 6e-04);.;Loss of disorder (P = 6e-04);.;
MVP
0.68
MPC
0.79
ClinPred
0.66
D
GERP RS
1.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.36
gMVP
0.73

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: rs11554940; hg19: chr19-49119177; API