17-39200346-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_SupportingPM2

The NM_000981.4(RPL19):​c.2T>G​(p.Met1?) variant causes a start lost change. 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)
Exomes 𝑓: 0.0000050 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RPL19
NM_000981.4 start_lost

Scores

7
7
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04
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 3 ACMG points.

PVS1
Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 3 codons. Genomic position: 39201214. Lost 0.012 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPL19NM_000981.4 linkc.2T>G p.Met1? start_lost Exon 1 of 6 ENST00000225430.9 NP_000972.1
RPL19NM_001330200.1 linkc.-399T>G 5_prime_UTR_variant Exon 1 of 6 NP_001317129.1
LOC124903996XR_007065745.1 linkn.763A>C non_coding_transcript_exon_variant Exon 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPL19ENST00000225430.9 linkc.2T>G p.Met1? start_lost Exon 1 of 6 1 NM_000981.4 ENSP00000225430.4 P84098

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000496
AC:
7
AN:
1412562
Hom.:
0
Cov.:
31
AF XY:
0.00000572
AC XY:
4
AN XY:
699720
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000270
Gnomad4 SAS exome
AF:
0.0000125
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000367
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Dec 04, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change affects the initiator methionine of the RPL19 mRNA. The next in-frame methionine is located at codon 3. This variant is not present in population databases (gnomAD no frequency). 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: 964835). 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
BayesDel_addAF
Pathogenic
0.47
D
BayesDel_noAF
Pathogenic
0.44
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.49
T;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Pathogenic
0.62
D
MetaRNN
Pathogenic
0.97
D;D
MetaSVM
Benign
-0.73
T
PROVEAN
Uncertain
-4.2
D;.
REVEL
Uncertain
0.52
Sift
Pathogenic
0.0
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.82
P;.
Vest4
0.92
MutPred
0.80
Gain of methylation at M1 (P = 0.0221);Gain of methylation at M1 (P = 0.0221);
MVP
0.72
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.98
gMVP
0.83

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.

Other links and lift over

dbSNP: rs1170075353; hg19: chr17-37356599; API