chr20-62387853-T-C

Variant names:

• chr20-62387853-T-C
• rs1987794737
• NM_001024.4:c.125T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001024.4(RPS21):​c.125T>C​(p.Val42Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. V42G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPS21 NM_001024.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 0 publications found

Genes affected

RPS21 (HGNC:10409): (ribosomal protein S21) 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 40S subunit. The protein belongs to the S21E family of ribosomal proteins. It is located in the cytoplasm. Alternative splice variants that encode different protein isoforms have been described, but their existence has not been verified. 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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07278705).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024.4. 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
	RPS21	NM_001024.4	MANE Select	c.125T>C	p.Val42Ala	missense	Exon 4 of 6	NP_001015.1	Q6FGH5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS21	ENST00000343986.9	TSL:1 MANE Select	c.125T>C	p.Val42Ala	missense	Exon 4 of 6	ENSP00000345957.3	P63220
	RPS21	ENST00000450116.6	TSL:1	c.125T>C	p.Val42Ala	missense	Exon 3 of 4	ENSP00000388332.2	Q8WVC2
	RPS21	ENST00000492356.2	TSL:1	n.157T>C		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.87
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.6
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.048
Sift	Benign	0.76	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.38
MutPred		0.29		Loss of stability (P = 0.0813)
MVP		0.12
MPC		1.2
ClinPred		0.036	T
GERP RS		1.5
Varity_R		0.14
gMVP		0.83
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs1987794737; hg19: chr20-60962909;