Genetic Variant RPL18A:p.Ser71Cys (chr19-17862107-C-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM1BP4BS2

The NM_000980.4(RPL18A):c.212C>G(p.Ser71Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,459,570 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. S71Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

RPL18A
NM_000980.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.65

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: Likely_benign. The variant received -3 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity RL18A_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.38376713).

BS2

High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL18A	NM_000980.4 link	c.212C>G	p.Ser71Cys	missense_variant	Exon 3 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.212C>G	p.Ser71Cys	missense_variant	Exon 3 of 5	1	NM_000980.4	ENSP00000222247.4		Q02543

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000805

AC:

AN:

248476

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

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:

0.0000116

AC:

AN:

1459570

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

726100

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33404

American (AMR)

AF:

0.0000671

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53352

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4190

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1111758

Other (OTH)

AF:

0.00

AC:

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

T;.;.;T;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.62

T;T;T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.38

T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.4

L;.;.;.;.

PhyloP100

4.7

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.9

D;.;.;.;.

REVEL

Benign

0.075

Sift

Benign

0.11

T;.;.;.;.

Sift4G

Benign

0.079

T;T;T;T;T

Polyphen

0.72

P;.;.;.;.

Vest4

0.61

MutPred

0.46

Gain of methylation at K70 (P = 0.0227);Gain of methylation at K70 (P = 0.0227);.;.;.;

MVP

0.23

MPC

0.88

ClinPred

0.51

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.46

Mutation Taster

=56/44

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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19-17862107-C-G

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