2-55235458-C-A

Position:

• chr2-55235458-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002954.6(RPS27A):​c.352C>A​(p.Arg118Ser) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS27A NM_002954.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.18

Genes affected

RPS27A (HGNC:10417): (ribosomal protein S27a) Ubiquitin, a highly conserved protein that has a major role in targeting cellular proteins for degradation by the 26S proteosome, is synthesized as a precursor protein consisting of either polyubiquitin chains or a single ubiquitin fused to an unrelated protein. This gene encodes a fusion protein consisting of ubiquitin at the N terminus and ribosomal protein S27a at the C terminus. When expressed in yeast, the protein is post-translationally processed, generating free ubiquitin monomer and ribosomal protein S27a. Ribosomal protein S27a is a component of the 40S subunit of the ribosome and belongs to the S27AE family of ribosomal proteins. It contains C4-type zinc finger domains and is located in the cytoplasm. Pseudogenes derived from this gene are present in the genome. As with ribosomal protein S27a, ribosomal protein L40 is also synthesized as a fusion protein with ubiquitin; similarly, ribosomal protein S30 is synthesized as a fusion protein with the ubiquitin-like protein fubi. Multiple alternatively spliced transcript variants that encode the same proteins have been identified.[provided by RefSeq, Sep 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.777

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS27A	NM_002954.6	c.352C>A	p.Arg118Ser	missense_variant	6/6	ENST00000272317.11	NP_002945.1
RPS27A	NM_001135592.2	c.352C>A	p.Arg118Ser	missense_variant	6/6		NP_001129064.1
RPS27A	NM_001177413.1	c.352C>A	p.Arg118Ser	missense_variant	5/5		NP_001170884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS27A	ENST00000272317.11	c.352C>A	p.Arg118Ser	missense_variant	6/6	1	NM_002954.6	ENSP00000272317	P1
RPS27A	ENST00000404735.1	c.352C>A	p.Arg118Ser	missense_variant	5/5	1		ENSP00000385659	P1
RPS27A	ENST00000402285.7	c.352C>A	p.Arg118Ser	missense_variant	6/6	3		ENSP00000383981	P1
RPS27A	ENST00000495843.1	n.1008C>A		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

RPS27A: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D;D;D
Eigen	Benign	0.099
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.96	.;.;D
M_CAP	Uncertain	0.092	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Pathogenic	3.9	H;H;H
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Uncertain	0.61
Sift	Uncertain	0.022	D;D;D
Sift4G	Uncertain	0.052	T;T;T
Polyphen		0.055	B;B;B
Vest4		0.80
MutPred		0.63		Gain of phosphorylation at R118 (P = 0.0235);Gain of phosphorylation at R118 (P = 0.0235);Gain of phosphorylation at R118 (P = 0.0235);
MVP		0.52
MPC		0.83
ClinPred		0.99	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.93
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-55462594;