Genetic Variant RPL18A:p.Ser4Ala (chr19-17859966-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000980.4(RPL18A):c.10T>G(p.Ser4Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,383,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

RPL18A
NM_000980.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1379112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL18A	NM_000980.4 link	c.10T>G	p.Ser4Ala	missense_variant	Exon 1 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.10T>G	p.Ser4Ala	missense_variant	Exon 1 of 5	1	NM_000980.4	ENSP00000222247.4		Q02543

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000217

AC:

AN:

138220

AF XY:

0.0000267

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000138

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:

0.00000217

AC:

AN:

1383184

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

682884

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29568

American (AMR)

AF:

0.0000893

AC:

AN:

33596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24620

East Asian (EAS)

AF:

0.00

AC:

AN:

33216

South Asian (SAS)

AF:

0.00

AC:

AN:

77832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48706

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4200

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074254

Other (OTH)

AF:

0.00

AC:

AN:

57192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000946

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 17, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.10T>G (p.S4A) alteration is located in exon 1 (coding exon 1) of the RPL18A gene. This alteration results from a T to G substitution at nucleotide position 10, causing the serine (S) at amino acid position 4 to be replaced by an alanine (A). 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

Benign

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.042

T;.;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.067

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.6

L;.;.

PhyloP100

2.6

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.90

N;.;.

REVEL

Benign

0.17

Sift

Benign

0.33

T;.;.

Sift4G

Benign

0.44

T;T;D

Polyphen

0.0

B;.;.

Vest4

0.41

MutPred

0.19

Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.33

MPC

0.78

ClinPred

0.41

GERP RS

3.4

PromoterAI

-0.014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.23

Mutation Taster

=90/10

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over