rs587777527

Positions:

• chr13-27254247-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_000982.4(RPL21):​c.95G>A​(p.Arg32Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,224 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RPL21 NM_000982.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-27254247-G-A is Pathogenic according to our data. Variant chr13-27254247-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 139638.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL21	NM_000982.4	c.95G>A	p.Arg32Gln	missense_variant	3/6	ENST00000311549.11	NP_000973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL21	ENST00000311549.11	c.95G>A	p.Arg32Gln	missense_variant	3/6	1	NM_000982.4	ENSP00000346027.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1447224 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 721040

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypotrichosis 12 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T;T;T;.
Eigen	Benign	0.059
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	.;.;.;T;T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.51	D;D;D;D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.70	N;N;N;N;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.8	N;N;N;N;.
REVEL	Uncertain	0.42
Sift	Benign	0.17	T;T;T;T;.
Sift4G	Benign	0.41	T;T;T;T;T
Polyphen		0.0090	B;B;B;B;.
Vest4		0.81
MutPred		0.48		Gain of catalytic residue at R32 (P = 0.0055);Gain of catalytic residue at R32 (P = 0.0055);Gain of catalytic residue at R32 (P = 0.0055);Gain of catalytic residue at R32 (P = 0.0055);Gain of catalytic residue at R32 (P = 0.0055);
MVP		0.94
MPC		1.2
ClinPred		0.90	D
GERP RS		5.0
Varity_R		0.38
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.50		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.50		Position offset: -27

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs587777527; hg19: chr13-27828384; COSMIC: COSV55388511; COSMIC: COSV55388511;