17-39201268-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000981.4(RPL19):​c.61A>G​(p.Lys21Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

RPL19
NM_000981.4 missense

Scores

9
8
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.06
Variant links:
Genes affected
RPL19 (HGNC:10312): (ribosomal protein L19) 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 ribosomal protein that is a component of the 60S subunit. The protein belongs to the L19E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPL19NM_000981.4 linkc.61A>G p.Lys21Glu missense_variant Exon 2 of 6 ENST00000225430.9 NP_000972.1
RPL19NM_001330200.1 linkc.55A>G p.Lys19Glu missense_variant Exon 2 of 6 NP_001317129.1
LOC124903996XR_007065745.1 linkn.-54T>C upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPL19ENST00000225430.9 linkc.61A>G p.Lys21Glu missense_variant Exon 2 of 6 1 NM_000981.4 ENSP00000225430.4 P84098

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151740
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000289
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
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151740
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74062
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000289
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Aug 03, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant has not been reported in the literature in individuals affected with RPL19-related conditions. This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 21 of the RPL19 protein (p.Lys21Glu). This variant is not present in population databases (gnomAD no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.48
D
BayesDel_noAF
Pathogenic
0.46
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.56
D;.;.;.
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.78
T;T;.;T
M_CAP
Uncertain
0.19
D
MetaRNN
Pathogenic
0.87
D;D;D;D
MetaSVM
Uncertain
0.37
D
MutationAssessor
Pathogenic
3.5
M;.;.;.
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-3.5
D;.;.;.
REVEL
Pathogenic
0.65
Sift
Uncertain
0.0010
D;.;.;.
Sift4G
Uncertain
0.013
D;D;D;D
Polyphen
0.99
D;.;.;.
Vest4
0.92
MutPred
0.57
Loss of methylation at K21 (P = 0.0032);.;.;.;
MVP
0.86
MPC
2.3
ClinPred
0.99
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8
Varity_R
0.81
gMVP
0.97

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.

Other links and lift over

dbSNP: rs1168491573; hg19: chr17-37357521; API