Genetic Variant RPL21:p.Lys122Asn (chr13-27256307-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000982.4(RPL21):c.366A>C(p.Lys122Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K122K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RPL21
NM_000982.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00300

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27650324).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000982.4. 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
	RPL21	NM_000982.4	MANE Select	c.366A>C	p.Lys122Asn	missense	Exon 5 of 6	NP_000973.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPL21	ENST00000311549.11	TSL:1 MANE Select	c.366A>C	p.Lys122Asn	missense	Exon 5 of 6	ENSP00000346027.4	P46778
RPL21	ENST00000939435.1		c.426A>C	p.Lys142Asn	missense	Exon 4 of 5	ENSP00000609494.1
RPL21	ENST00000939430.1		c.384A>C	p.Lys128Asn	missense	Exon 5 of 6	ENSP00000609489.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457008

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724834

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33104

American (AMR)

AF:

0.00

AC:

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39378

South Asian (SAS)

AF:

0.00

AC:

AN:

85732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53280

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108870

Other (OTH)

AF:

0.00

AC:

AN:

60170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.84

M_CAP

Benign

0.020

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.3

PhyloP100

0.0030

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.24

Sift

Benign

0.062

Sift4G

Benign

0.070

Polyphen

0.0010

Vest4

0.26

MutPred

0.33

Loss of methylation at K122 (P = 0.011)

MVP

0.85

MPC

1.3

ClinPred

0.82

GERP RS

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.69

Mutation Taster

=58/42

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over