1-92832116-T-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_000969.5(RPL5):c.2T>G(p.Met1?) variant causes a start lost, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
RPL5
NM_000969.5 start_lost, splice_region
NM_000969.5 start_lost, splice_region
Scores
9
6
1
Splicing: ADA: 0.9545
1
1
Clinical Significance
Conservation
PhyloP100: 4.50
Genes affected
RPL5 (HGNC:10360): (ribosomal protein L5) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the L18P family of ribosomal proteins and component of the 60S subunit. The encoded protein binds 5S rRNA to form a stable complex called the 5S ribonucleoprotein particle (RNP), which is necessary for the transport of nonribosome-associated cytoplasmic 5S rRNA to the nucleolus for assembly into ribosomes. The encoded protein may also function to inhibit tumorigenesis through the activation of downstream tumor suppressors and the downregulation of oncoprotein expression. Mutations in this gene have been identified in patients with Diamond-Blackfan Anemia (DBA). This gene is co-transcribed with the small nucleolar RNA gene U21, which is located in its fifth intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. [provided by RefSeq, Mar 2017]
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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;
PP5
Variant 1-92832116-T-G is Pathogenic according to our data. Variant chr1-92832116-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 2202776.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-92832116-T-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL5 | NM_000969.5 | c.2T>G | p.Met1? | start_lost, splice_region_variant | 1/8 | ENST00000370321.8 | |
RPL5 | NR_146333.1 | n.131T>G | splice_region_variant, non_coding_transcript_exon_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL5 | ENST00000370321.8 | c.2T>G | p.Met1? | start_lost, splice_region_variant | 1/8 | 1 | NM_000969.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Diamond-Blackfan anemia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 22, 2022 | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Disruption of the initiator codon has been observed in individuals with Diamond-Blackfan anemia (PMID: 19773262, 20378560, 20960466, 30503522; Invitae). This sequence change affects the initiator methionine of the RPL5 mRNA. The next in-frame methionine is located at codon 51. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PROVEAN
Uncertain
.;D;.
REVEL
Pathogenic
Sift
Pathogenic
.;D;.
Sift4G
Pathogenic
.;D;.
Polyphen
D;D;.
Vest4
0.97
MutPred
Gain of methylation at M1 (P = 0.0091);Gain of methylation at M1 (P = 0.0091);Gain of methylation at M1 (P = 0.0091);
MVP
0.98
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.