Variant 19-17863001-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000980.4(RPL18A):c.412C>T(p.Arg138Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000788 in 1,611,778 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

RPL18A
NM_000980.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.80

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL18A	NM_000980.4 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	4/5	ENST00000222247.10	NP_000971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL18A	ENST00000222247.10 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	4/5	1	NM_000980.4	ENSP00000222247	P1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000769

AC:

AN:

247018

Hom.:

AF XY:

0.0000894

AC XY:

AN XY:

134264

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000154

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000788

AC:

115

AN:

1459638

Hom.:

Cov.:

AF XY:

0.0000744

AC XY:

AN XY:

726152

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000954

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000660

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.0000989

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

May 08, 2023

The c.412C>T (p.R138C) alteration is located in exon 4 (coding exon 4) of the RPL18A gene. This alteration results from a C to T substitution at nucleotide position 412, causing the arginine (R) at amino acid position 138 to be replaced by a cysteine (C). 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

0.97

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.37

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;.;.;T;T

Eigen

Benign

0.057

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D;D;D;D

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.74

D;D;D;D;D

MetaSVM

Benign

-0.51

MutationAssessor

Benign

2.0

M;.;.;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-7.3

D;.;.;.;.

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

D;.;.;.;.

Sift4G

Uncertain

0.018

D;D;D;D;D

Polyphen

0.0090

B;.;.;.;.

Vest4

0.91

MVP

0.64

MPC

1.2

ClinPred

0.50

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.85

gMVP

0.71

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.

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