RPS6 p.Leu213Phe

Variant names:

• chr9-19376509-C-A
• NM_001010.3:c.639G>T
• RPS6 p.Leu213Phe

Your query was ambiguous. Multiple possible variants found:

• chr9-19376509-C-A
• chr9-19376509-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001010.3(RPS6):​c.639G>T​(p.Leu213Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS6 NM_001010.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.68
• Publications: 0 publications found

Genes affected

RPS6 (HGNC:10429): (ribosomal protein S6) 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 cytoplasmic ribosomal protein that is a component of the 40S subunit. The protein belongs to the S6E family of ribosomal proteins. It is the major substrate of protein kinases in the ribosome, with subsets of five C-terminal serine residues phosphorylated by different protein kinases. Phosphorylation is induced by a wide range of stimuli, including growth factors, tumor-promoting agents, and mitogens. Dephosphorylation occurs at growth arrest. The protein may contribute to the control of cell growth and proliferation through the selective translation of particular classes of mRNA. 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010.3. 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
	RPS6	NM_001010.3	MANE Select	c.639G>T	p.Leu213Phe	missense	Exon 5 of 6	NP_001001.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6	ENST00000380394.9	TSL:1 MANE Select	c.639G>T	p.Leu213Phe	missense	Exon 5 of 6	ENSP00000369757.4	P62753
	RPS6	ENST00000380384.5	TSL:1	c.546G>T	p.Leu182Phe	missense	Exon 4 of 5	ENSP00000369745.1	A2A3R5
	RPS6	ENST00000889073.1		c.663G>T	p.Leu221Phe	missense	Exon 5 of 6	ENSP00000559132.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.044	D
Varity_R		0.67
gMVP		0.64
Mutation Taster		=24/76	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-19376507;