Variant 22-39314788-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000216146.9(RPL3):c.747C>T(p.Arg249=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,613,752 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 12 hom. )

Consequence

RPL3
ENST00000216146.9 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.120

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 22-39314788-G-A is Benign according to our data. Variant chr22-39314788-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2653146.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.12 with no splicing effect.

BS2

High AC in GnomAd4 at 295 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL3	NM_000967.4 linkuse as main transcript	c.747C>T	p.Arg249=	synonymous_variant	6/10	ENST00000216146.9	NP_000958.1
RPL3	NM_001033853.2 linkuse as main transcript	c.600C>T	p.Arg200=	synonymous_variant	6/10		NP_001029025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL3	ENST00000216146.9 linkuse as main transcript	c.747C>T	p.Arg249=	synonymous_variant	6/10	1	NM_000967.4	ENSP00000346001	P1

Frequencies

GnomAD3 genomes

AF:

0.00194

AC:

295

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0145

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00185

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00233

AC:

586

AN:

251332

Hom.:

AF XY:

0.00220

AC XY:

299

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.0183

Gnomad NFE exome

AF:

0.00146

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00165

AC:

2412

AN:

1461612

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

1191

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.0175

Gnomad4 NFE exome

AF:

0.00120

Gnomad4 OTH exome

AF:

0.00200

GnomAD4 genome

AF:

0.00194

AC:

295

AN:

152140

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0145

Gnomad4 NFE

AF:

0.00185

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00149

Hom.:

Bravo

AF:

0.000638

EpiCase

AF:

0.00120

EpiControl

AF:

0.00130

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

RPL3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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