Variant 16-1945869-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005061.3(RPL3L):c.1013C>G(p.Ala338Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00434 in 1,613,994 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 20 hom. )

Consequence

RPL3L
NM_005061.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.96

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022277802).

BP6

Variant 16-1945869-G-C is Benign according to our data. Variant chr16-1945869-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2498637.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.003 (457/152356) while in subpopulation NFE AF= 0.00487 (331/68032). AF 95% confidence interval is 0.00443. There are 2 homozygotes in gnomad4. There are 210 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL3L	NM_005061.3 linkuse as main transcript	c.1013C>G	p.Ala338Gly	missense_variant	8/10	ENST00000268661.8	NP_005052.1	Q92901
RPL3L	XM_011522571.3 linkuse as main transcript	c.1028C>G	p.Ala343Gly	missense_variant	8/10		XP_011520873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL3L	ENST00000268661.8 linkuse as main transcript	c.1013C>G	p.Ala338Gly	missense_variant	8/10	1	NM_005061.3	ENSP00000268661.7		Q92901

Frequencies

GnomAD3 genomes

AF:

0.00301

AC:

458

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00488

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00287

AC:

722

AN:

251226

Hom.:

AF XY:

0.00300

AC XY:

407

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.000862

Gnomad AMR exome

AF:

0.00229

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.00512

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00448

AC:

6553

AN:

1461638

Hom.:

Cov.:

AF XY:

0.00432

AC XY:

3142

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00122

Gnomad4 NFE exome

AF:

0.00547

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

AF:

0.00300

AC:

457

AN:

152356

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

210

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00487

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00293

Hom.:

Bravo

AF:

0.00340

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00295

AC:

358

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00382

EpiControl

AF:

0.00480

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, 2024

RPL3L: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.11

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0076

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.65

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.2

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Sift4G

Benign

0.21

Polyphen

0.30

Vest4

0.46

MVP

0.58

MPC

0.11

ClinPred

0.089

GERP RS

3.3

Varity_R

0.36

gMVP

0.51

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