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

Variant summary

Our verdict is Likely benign. Variant got -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.

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

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250832

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135796

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 SAS exome

AF:

0.0000327

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000628

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

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;.

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over