22-39313642-G-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_000967.4(RPL3):c.1039C>T(p.Leu347Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000954 in 1,613,612 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

RPL3
NM_000967.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.14

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:

SNORD83B (HGNC:17132): (small nucleolar RNA, C/D box 83B) Intronic regions of ribosomal protein genes can harbor noncoding small nucleolar RNAs (snoRNAs), like SNORD83B, 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 SNORD83B, function in 2-prime-O-ribose methylation of rRNAs (Duga et al., 2000 [PubMed 10684968]).[supplied by OMIM, Mar 2008]

SNORD83B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.8

BS2

High AC in GnomAdExome4 at 150 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL3	NM_000967.4 link	c.1039C>T	p.Leu347Phe	missense_variant	Exon 8 of 10	ENST00000216146.9	NP_000958.1	P39023
RPL3	NM_001033853.2 link	c.892C>T	p.Leu298Phe	missense_variant	Exon 8 of 10		NP_001029025.1	Q96QL0B3KS36
SNORD83B	NR_000028.1 link	n.*177C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL3	ENST00000216146.9 link	c.1039C>T	p.Leu347Phe	missense_variant	Exon 8 of 10	1	NM_000967.4	ENSP00000346001.3		P39023

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000996

AC:

AN:

251064

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000103

AC:

150

AN:

1461398

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000863

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1039C>T (p.L347F) alteration is located in exon 8 (coding exon 8) of the RPL3 gene. This alteration results from a C to T substitution at nucleotide position 1039, causing the leucine (L) at amino acid position 347 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

.;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.073

MetaRNN

Pathogenic

0.80

D;D

MetaSVM

Benign

-0.41

MutationAssessor

Pathogenic

3.1

.;M

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.011

D;D

Sift4G

Benign

0.16

T;T

Polyphen

0.96

D;P

Vest4

0.89

MutPred

0.73

.;Gain of methylation at K349 (P = 0.0657);

MVP

0.56

MPC

1.3

ClinPred

0.69

GERP RS

5.2

Varity_R

0.50

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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