Genetic Variant RPL3:c.366-70C>A (chr22-39316911-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000967.4(RPL3):c.366-70C>A variant causes a intron change. The variant allele was found at a frequency of 0.000000687 in 1,454,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RPL3
NM_000967.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.47

Publications

0 publications found

Variant links:

Genes affected

RPL3 (HGNC:10332): (ribosomal protein L3) Ribosomes, the complexes 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 L3P family of ribosomal proteins and it is located in the cytoplasm. The protein can bind to the HIV-1 TAR mRNA, and it has been suggested that the protein contributes to tat-mediated transactivation. This gene is co-transcribed with several small nucleolar RNA genes, which are located in several of this gene's introns. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. 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]

RPL3 links:

SNORD139 (HGNC:50421): (small nucleolar RNA, C/D box 139) Intronic regions of ribosomal protein genes can harbor noncoding small nucleolar RNAs (snoRNAs), like U86, which are generated during pre-mRNA processing. snoRNAs form part of the small nucleolar ribonucleoprotein particles (snoRNPs) involved in pre-rRNA processing and modification. snoRNAs of the box C/D class, like U86, function in 2-prime-O-ribose methylation of rRNAs (Duga et al., 2000 [PubMed 10684968]).[supplied by OMIM, Mar 2008]

SNORD139 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000967.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL3	NM_000967.4	MANE Select	c.366-70C>A	intron	N/A	NP_000958.1	P39023
RPL3	NM_001033853.2		c.366-70C>A	intron	N/A	NP_001029025.1
SNORD139	NR_000026.1		n.-15C>A	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPL3	ENST00000216146.9	TSL:1 MANE Select	c.366-70C>A	intron	N/A	ENSP00000346001.3	P39023
RPL3	ENST00000401609.5	TSL:1	c.210-70C>A	intron	N/A	ENSP00000386101.1	G5E9G0
RPL3	ENST00000465618.5	TSL:1	n.1136C>A	non_coding_transcript_exon	Exon 4 of 10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454902

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724102

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33340

American (AMR)

AF:

0.00

AC:

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.00

AC:

AN:

86096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106750

Other (OTH)

AF:

0.00

AC:

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

6.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over