Genetic Variant RPL21:p.Arg102Gln (chr13-27256246-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000982.4(RPL21):c.305G>A(p.Arg102Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000488 in 1,434,674 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

RPL21
NM_000982.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.79

Publications

0 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 Gene-Disease associations (from GenCC):

hypotrichosis 12
Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
hypotrichosis simplex
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RPL21 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL21	NM_000982.4 link	c.305G>A	p.Arg102Gln	missense_variant	Exon 5 of 6	ENST00000311549.11	NP_000973.2	P46778Q6IAX2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL21	ENST00000311549.11 link	c.305G>A	p.Arg102Gln	missense_variant	Exon 5 of 6	1	NM_000982.4	ENSP00000346027.4		P46778

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000434

AC:

AN:

230636

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000299

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:

0.00000488

AC:

AN:

1434674

Hom.:

Cov.:

AF XY:

0.00000420

AC XY:

AN XY:

713944

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32518

American (AMR)

AF:

0.0000228

AC:

AN:

43824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25854

East Asian (EAS)

AF:

0.00

AC:

AN:

39000

South Asian (SAS)

AF:

0.00

AC:

AN:

84254

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4742

European-Non Finnish (NFE)

AF:

0.00000366

AC:

AN:

1092330

Other (OTH)

AF:

0.0000169

AC:

AN:

59270

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

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 19, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.305G>A (p.R102Q) alteration is located in exon 5 (coding exon 4) of the RPL21 gene. This alteration results from a G to A substitution at nucleotide position 305, causing the arginine (R) at amino acid position 102 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

T;T;T;T;.

Eigen

Benign

0.038

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.75

.;.;.;T;T

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.47

T;T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.3

L;L;L;L;.

PhyloP100

7.8

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.4

D;D;D;D;.

REVEL

Uncertain

0.40

Sift

Benign

0.074

T;T;T;T;.

Sift4G

Benign

0.18

T;T;T;T;T

Polyphen

0.023

B;B;B;B;.

Vest4

0.51

MutPred

0.40

Gain of catalytic residue at K100 (P = 0.0099);Gain of catalytic residue at K100 (P = 0.0099);Gain of catalytic residue at K100 (P = 0.0099);Gain of catalytic residue at K100 (P = 0.0099);Gain of catalytic residue at K100 (P = 0.0099);

MVP

0.97

MPC

1.2

ClinPred

0.87

GERP RS

4.0

Varity_R

0.48

gMVP

0.65

Mutation Taster

=40/60

disease causing

(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

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chr13-27256246-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over