17-39201253-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BS2

The NM_000981.4(RPL19):c.46C>T(p.Arg16Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,612,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RPL19
NM_000981.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83

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]

RPL19 links:

LOC124903996 (HGNC:):

LOC124903996 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM1

In a modified_residue Citrulline (size 0) in uniprot entity RL19_HUMAN

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RPL19	NM_000981.4 link	c.46C>T	p.Arg16Cys	missense_variant	Exon 2 of 6	ENST00000225430.9	NP_000972.1
RPL19	NM_001330200.1 link	c.40C>T	p.Arg14Cys	missense_variant	Exon 2 of 6		NP_001317129.1
LOC124903996	XR_007065745.1 link	n.-39G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL19	ENST00000225430.9 link	c.46C>T	p.Arg16Cys	missense_variant	Exon 2 of 6	1	NM_000981.4	ENSP00000225430.4		P84098

Frequencies

GnomAD3 genomes

AF:

0.0000529

AC:

AN:

151192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.00

Gnomad OTH

AF:

0.000484

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

249530

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461700

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000529

AC:

AN:

151192

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

73696

show subpopulations

Gnomad4 AFR

AF:

0.000122

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000484

Alfa

AF:

0.0000709

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000331

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jul 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 16 of the RPL19 protein (p.Arg16Cys). This variant is present in population databases (rs774934686, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RPL19-related conditions. ClinVar contains an entry for this variant (Variation ID: 2175633). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

T;.;.;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.047

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

D;D;.;D

M_CAP

Benign

0.0036

MetaRNN

Uncertain

0.54

D;D;D;D

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.28

N;.;.;.

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-2.6

D;.;.;.

REVEL

Uncertain

0.45

Sift

Benign

0.11

T;.;.;.

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.0020

B;.;.;.

Vest4

0.62

MVP

0.65

MPC

1.4

ClinPred

0.50

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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