Genetic Variant RPL21:p.Gln79Glu (chr13-27255347-C-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_000982.4(RPL21):c.235C>G(p.Gln79Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000625 in 1,279,206 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q79K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

RPL21
NM_000982.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.79

Publications

1 publications found

Variant links:

Genes affected

RPL21 (HGNC:10313): (ribosomal protein L21) 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 L21E family of ribosomal proteins. It is located in the cytoplasm. 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]

RPL21 links:

SNORA27 (HGNC:32617): (small nucleolar RNA, H/ACA box 27)

SNORA27 links:

SNORD102 (HGNC:10099): (small nucleolar RNA, C/D box 102)

SNORD102 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.41234776).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL21	NM_000982.4 link	c.235C>G	p.Gln79Glu	missense_variant	Exon 4 of 6	ENST00000311549.11	NP_000973.2	P46778Q6IAX2
SNORA27	NR_002575.1 link	n.-54C>G		upstream_gene_variant
SNORD102	NR_002574.1 link	n.*212C>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL21	ENST00000311549.11 link	c.235C>G	p.Gln79Glu	missense_variant	Exon 4 of 6	1	NM_000982.4	ENSP00000346027.4		P46778

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152178

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:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250832

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000444

AC:

AN:

1126910

Hom.:

Cov.:

AF XY:

0.00000520

AC XY:

AN XY:

577012

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26874

American (AMR)

AF:

0.00

AC:

AN:

44328

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24066

East Asian (EAS)

AF:

0.00

AC:

AN:

38172

South Asian (SAS)

AF:

0.0000628

AC:

AN:

79628

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53232

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5132

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

806324

Other (OTH)

AF:

0.00

AC:

AN:

49154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

T;T;T;T;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

.;.;.;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.41

T;T;T;T;T

MetaSVM

Benign

-0.37

MutationAssessor

Pathogenic

3.1

M;M;M;M;.

PhyloP100

4.8

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.8

N;N;N;N;.

REVEL

Benign

0.26

Sift

Uncertain

0.015

D;D;D;D;.

Sift4G

Benign

0.15

T;T;T;T;T

Polyphen

0.015

B;B;B;B;.

Vest4

0.47

MutPred

0.43

Gain of catalytic residue at V75 (P = 0.0016);Gain of catalytic residue at V75 (P = 0.0016);Gain of catalytic residue at V75 (P = 0.0016);Gain of catalytic residue at V75 (P = 0.0016);Gain of catalytic residue at V75 (P = 0.0016);

MVP

0.77

MPC

2.0

ClinPred

0.94

GERP RS

4.8

Varity_R

0.62

gMVP

0.78

Mutation Taster

=74/26

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.

13-27255347-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over