16-1946958-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_005061.3(RPL3L):c.829C>T(p.Arg277Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000394 in 1,607,230 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R277H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00033 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00040 ( 0 hom. )

Consequence

RPL3L
NM_005061.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 9.94

Variant links:

Genes affected

RPL3L (HGNC:10351): (ribosomal protein L3 like) This gene encodes a protein that shares sequence similarity with ribosomal protein L3. The protein belongs to the L3P family of ribosomal proteins. Unlike the ubiquitous expression of ribosomal protein genes, this gene has a tissue-specific pattern of expression, with the highest levels of expression in skeletal muscle and heart. It is not currently known whether the encoded protein is a functional ribosomal protein or whether it has evolved a function that is independent of the ribosome. [provided by RefSeq, Jul 2008]

RPL3L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL3L	NM_005061.3 link	c.829C>T	p.Arg277Cys	missense_variant	Exon 6 of 10	ENST00000268661.8	NP_005052.1	Q92901
RPL3L	XM_011522571.3 link	c.844C>T	p.Arg282Cys	missense_variant	Exon 6 of 10		XP_011520873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL3L	ENST00000268661.8 link	c.829C>T	p.Arg277Cys	missense_variant	Exon 6 of 10	1	NM_005061.3	ENSP00000268661.7		Q92901

Frequencies

GnomAD3 genomes

AF:

0.000328

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000247

AC:

AN:

247116

AF XY:

0.000238

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.0000885

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000386

Gnomad NFE exome

AF:

0.000420

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000401

AC:

583

AN:

1454962

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

292

AN XY:

723504

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

AC:

AN:

33282

Gnomad4 AMR exome

AF:

0.0000907

AC:

AN:

44122

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26018

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39614

Gnomad4 SAS exome

AF:

0.0000232

AC:

AN:

86066

Gnomad4 FIN exome

AF:

0.000428

AC:

AN:

51406

Gnomad4 NFE exome

AF:

0.000483

AC:

536

AN:

1109800

Gnomad4 Remaining exome

AF:

0.000217

AC:

AN:

59988

Heterozygous variant carriers

123

164

205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

110

<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

AF:

0.000328

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0000241

AC:

0.0000241127

AN:

0.0000241127

Gnomad4 AMR

AF:

0.000131

AC:

0.000130804

AN:

0.000130804

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.000188

AC:

0.000188182

AN:

0.000188182

Gnomad4 NFE

AF:

0.000647

AC:

0.000646621

AN:

0.000646621

Gnomad4 OTH

AF:

0.000478

AC:

0.000477555

AN:

0.000477555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome 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

Alfa

AF:

0.000577

Hom.:

Bravo

AF:

0.000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000206

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.829C>T (p.R277C) alteration is located in exon 6 (coding exon 6) of the RPL3L gene. This alteration results from a C to T substitution at nucleotide position 829, causing the arginine (R) at amino acid position 277 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Cardiomyopathy, dilated, 2D

Uncertain:1

Apr 11, 2023

Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Heterozygous variant NM_005061.3:c.829C>T in RPL3L gene was found on the WES data in female proband (46 y.o., Caucasian) with obstructive HCM. The c.829C>T has AF=0,0002468 in The Genome Aggregation Database (gnomAD) (Date of access: 10-04-2023). Clinvar does not contain an entry for this variant. In accordance with ACMG(2015) criteria this variant is classified as a variant with uncertain significance with the following criteria selected: PM2, PP3. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.046

MetaRNN

Pathogenic

0.87

MetaSVM

Uncertain

-0.28

MutationAssessor

Pathogenic

3.5

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-7.4

REVEL

Uncertain

0.63

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.046

Polyphen

1.0

Vest4

0.84

MVP

0.80

MPC

0.20

ClinPred

0.61

GERP RS

4.9

Varity_R

0.68

gMVP

0.85

Mutation Taster

=47/53

disease causing

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

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