Genetic Variant RPL3:p.Pro37Pro (chr22-39318485-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000967.4(RPL3):c.111G>A(p.Pro37Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,613,294 control chromosomes in the GnomAD database, including 176,320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12614 hom., cov: 31)

Exomes 𝑓: 0.46 ( 163706 hom. )

Consequence

RPL3
NM_000967.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.440

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 22-39318485-C-T is Benign according to our data. Variant chr22-39318485-C-T is described in ClinVar as [Benign]. Clinvar id is 1258969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL3	NM_000967.4 link	c.111G>A	p.Pro37Pro	synonymous_variant	Exon 2 of 10	ENST00000216146.9	NP_000958.1	P39023
RPL3	NM_001033853.2 link	c.111G>A	p.Pro37Pro	synonymous_variant	Exon 2 of 10		NP_001029025.1	Q96QL0B3KS36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL3	ENST00000216146.9 link	c.111G>A	p.Pro37Pro	synonymous_variant	Exon 2 of 10	1	NM_000967.4	ENSP00000346001.3		P39023

Frequencies

GnomAD3 genomes

AF:

0.388

AC:

58881

AN:

151798

Hom.:

12613

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.498

Gnomad AMR

AF:

0.429

Gnomad ASJ

AF:

0.570

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.422

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.416

GnomAD3 exomes

AF:

0.413

AC:

103431

AN:

250594

Hom.:

23294

AF XY:

0.420

AC XY:

56931

AN XY:

135498

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.586

Gnomad EAS exome

AF:

0.105

Gnomad SAS exome

AF:

0.376

Gnomad FIN exome

AF:

0.428

Gnomad NFE exome

AF:

0.491

Gnomad OTH exome

AF:

0.451

GnomAD4 exome

AF:

0.464

AC:

678026

AN:

1461378

Hom.:

163706

Cov.:

AF XY:

0.462

AC XY:

336046

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.382

Gnomad4 ASJ exome

AF:

0.581

Gnomad4 EAS exome

AF:

0.0754

Gnomad4 SAS exome

AF:

0.380

Gnomad4 FIN exome

AF:

0.434

Gnomad4 NFE exome

AF:

0.495

Gnomad4 OTH exome

AF:

0.448

GnomAD4 genome

AF:

0.388

AC:

58892

AN:

151916

Hom.:

12614

Cov.:

AF XY:

0.382

AC XY:

28382

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.218

Gnomad4 AMR

AF:

0.428

Gnomad4 ASJ

AF:

0.570

Gnomad4 EAS

AF:

0.108

Gnomad4 SAS

AF:

0.366

Gnomad4 FIN

AF:

0.422

Gnomad4 NFE

AF:

0.488

Gnomad4 OTH

AF:

0.411

Alfa

AF:

0.467

Hom.:

5635

Bravo

AF:

0.379

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 05, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

4.6

DANN

Benign

0.88

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