chr1-92832069-C-G
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_000969.5(RPL5):c.-46C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
RPL5
NM_000969.5 5_prime_UTR
NM_000969.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.833
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 Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BS2
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL5 | NM_000969.5 | c.-46C>G | 5_prime_UTR_variant | 1/8 | ENST00000370321.8 | ||
RPL5 | NR_146333.1 | n.84C>G | non_coding_transcript_exon_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL5 | ENST00000370321.8 | c.-46C>G | 5_prime_UTR_variant | 1/8 | 1 | NM_000969.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152264Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000404 AC: 10AN: 247536Hom.: 0 AF XY: 0.0000447 AC XY: 6AN XY: 134288
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GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461140Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 726822
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74392
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Diamond-Blackfan anemia 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at