Genetic Variant RPL39:p.Arg11Gln (chrX-119789983-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001000.4(RPL39):c.32G>A(p.Arg11Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000196 in 1,171,232 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000020 ( 0 hom. 10 hem. )

Consequence

RPL39
NM_001000.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69

Publications

0 publications found

Variant links:

Genes affected

RPL39 (HGNC:10350): (ribosomal protein L39) Ribosomes, the organelles 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 S39E family of ribosomal proteins. It is located in the cytoplasm. In rat, the protein is the smallest, and one of the most basic, proteins of the ribosome. This gene is co-transcribed with the U69 small nucleolar RNA gene, which is located in its second intron. 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]

RPL39 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1663914).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001000.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL39	NM_001000.4	MANE Select	c.32G>A	p.Arg11Gln	missense	Exon 2 of 3	NP_000991.1	P62891

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL39	ENST00000361575.4	TSL:1 MANE Select	c.32G>A	p.Arg11Gln	missense	Exon 2 of 3	ENSP00000355315.3	P62891
RPL39	ENST00000468844.1	TSL:1	n.1613G>A		non_coding_transcript_exon	Exon 1 of 2
RPL39	ENST00000949343.1		c.71G>A	p.Arg24Gln	missense	Exon 2 of 3	ENSP00000619402.1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111525

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.000664

GnomAD2 exomes

AF:

0.0000166

AC:

AN:

180371

AF XY:

0.0000456

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1059707

Hom.:

Cov.:

AF XY:

0.0000302

AC XY:

AN XY:

331109

show subpopulations

African (AFR)

AF:

0.000156

AC:

AN:

25707

American (AMR)

AF:

0.00

AC:

AN:

35126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19156

East Asian (EAS)

AF:

0.00

AC:

AN:

30079

South Asian (SAS)

AF:

0.0000188

AC:

AN:

53256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4044

European-Non Finnish (NFE)

AF:

0.0000173

AC:

AN:

809492

Other (OTH)

AF:

0.0000446

AC:

AN:

44869

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111525

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

33715

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30691

American (AMR)

AF:

0.00

AC:

AN:

10359

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3566

South Asian (SAS)

AF:

0.00

AC:

AN:

2708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53150

Other (OTH)

AF:

0.000664

AC:

AN:

1505

Age Distribution

Genome Hom

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:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

0.0026

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.031

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.73

M_CAP

Benign

0.011

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

PhyloP100

5.7

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.63

REVEL

Uncertain

0.29

Sift

Benign

0.85

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.12

MutPred

0.41

Gain of methylation at K15 (P = 0.1093)

MVP

0.88

MPC

1.7

ClinPred

0.95

GERP RS

4.8

Varity_R

0.21

gMVP

0.85

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over