19-17862185-A-G

Variant names:

• chr19-17862185-A-G
• NM_000980.4:c.290A>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_000980.4(RPL18A):​c.290A>G​(p.Tyr97Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPL18A NM_000980.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.05
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.972

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL18A	NM_000980.4	c.290A>G	p.Tyr97Cys	missense_variant	Exon 3 of 5	ENST00000222247.10	NP_000971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL18A	ENST00000222247.10	c.290A>G	p.Tyr97Cys	missense_variant	Exon 3 of 5	1	NM_000980.4	ENSP00000222247.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.290A>G (p.Y97C) alteration is located in exon 3 (coding exon 3) of the RPL18A gene. This alteration results from a A to G substitution at nucleotide position 290, causing the tyrosine (Y) at amino acid position 97 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	0.98
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T;.;.;T;T
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.063	D
MetaRNN	Pathogenic	0.97	D;D;D;D;D
MetaSVM	Uncertain	-0.030	T
MutationAssessor	Uncertain	2.4	M;.;.;.;.
PhyloP100		9.1
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-8.2	D;.;.;.;.
REVEL	Uncertain	0.56
Sift	Pathogenic	0.0	D;.;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	D;.;.;.;.
Vest4		0.97
MutPred		0.89		Loss of phosphorylation at Y97 (P = 0.0554);Loss of phosphorylation at Y97 (P = 0.0554);.;.;.;
MVP		0.79
MPC		2.0
ClinPred		1.0	D
GERP RS		4.2
Varity_R		0.92
gMVP		0.79
Mutation Taster		=16/84	disease causing

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

Other links and lift over

hg19: chr19-17972994;