Genetic Variant RPL18A:p.Arg161Leu (chr19-17863214-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000980.4(RPL18A):c.482G>T(p.Arg161Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R161H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPL18A
NM_000980.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.72

Publications

0 publications found

Variant links:

Genes affected

RPL18A (HGNC:10311): (ribosomal protein L18a) 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 L18AE family of ribosomal proteins that is a component of the 60S subunit. The encoded protein may play a role in viral replication by interacting with the hepatitis C virus internal ribosome entry site (IRES). This gene is co-transcribed with the U68 snoRNA, located within the third intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. [provided by RefSeq, Jul 2012]

RPL18A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3346387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL18A	NM_000980.4 link	c.482G>T	p.Arg161Leu	missense_variant	Exon 5 of 5	ENST00000222247.10	NP_000971.1	Q02543

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL18A	ENST00000222247.10 link	c.482G>T	p.Arg161Leu	missense_variant	Exon 5 of 5	1	NM_000980.4	ENSP00000222247.4		Q02543

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249314

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.0000629

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000137

AC:

AN:

1459216

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725932

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33404

American (AMR)

AF:

0.00

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86134

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4428

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111284

Other (OTH)

AF:

0.00

AC:

AN:

60132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.22

T;.;T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.21

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.59

T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.33

T;T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.1

L;.;.;.

PhyloP100

5.7

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.6

D;.;.;.

REVEL

Benign

0.24

Sift

Benign

0.055

T;.;.;.

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.0010

B;.;.;.

Vest4

0.64

MutPred

0.33

Loss of solvent accessibility (P = 0.0052);.;.;.;

MVP

0.66

MPC

1.1

ClinPred

0.32

GERP RS

3.6

Varity_R

0.53

gMVP

0.44

Mutation Taster

=17/83

disease causing

(source)

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

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19-17863214-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over