Variant 19-48615398-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000979.4(RPL18):c.541C>T(p.Arg181Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,436 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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RPL18
NM_000979.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.234

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]

RPL18 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.8

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RPL18	NM_000979.4 linkuse as main transcript	c.541C>T	p.Arg181Trp	missense_variant	7/7	ENST00000549920.6
RPL18	NM_001270490.2 linkuse as main transcript	c.454C>T	p.Arg152Trp	missense_variant	6/6
RPL18	NR_073022.2 linkuse as main transcript	n.568C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL18	ENST00000549920.6 linkuse as main transcript	c.541C>T	p.Arg181Trp	missense_variant	7/7	1	NM_000979.4	P1	Q07020-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250964

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135662

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:

6.85e-7

AC:

AN:

1460436

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726346

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Jan 31, 2024

The c.541C>T (p.R181W) alteration is located in exon 7 (coding exon 7) of the RPL18 gene. This alteration results from a C to T substitution at nucleotide position 541, causing the arginine (R) at amino acid position 181 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

0.99

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.60

D;T;.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.80

D;D;D;D

MetaSVM

Uncertain

0.27

MutationAssessor

Pathogenic

3.0

M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-6.6

D;D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0080

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.98

D;.;.;.

Vest4

0.80

MutPred

0.63

Loss of methylation at R181 (P = 0.0177);.;.;.;

MVP

0.74

MPC

0.80

ClinPred

0.97

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.48

gMVP

0.57

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over