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GeneBe

2-55234867-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_002954.6(RPS27A):c.226G>A(p.Gly76Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RPS27A
NM_002954.6 missense

Scores

5
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.94
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1
In a mutagenesis_site Loss of ADP-ribosylation. (size 0) in uniprot entity RS27A_HUMAN
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS27ANM_002954.6 linkuse as main transcriptc.226G>A p.Gly76Ser missense_variant 5/6 ENST00000272317.11
RPS27ANM_001135592.2 linkuse as main transcriptc.226G>A p.Gly76Ser missense_variant 5/6
RPS27ANM_001177413.1 linkuse as main transcriptc.226G>A p.Gly76Ser missense_variant 4/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS27AENST00000272317.11 linkuse as main transcriptc.226G>A p.Gly76Ser missense_variant 5/61 NM_002954.6 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 09, 2022The c.226G>A (p.G76S) alteration is located in exon 5 (coding exon 4) of the RPS27A gene. This alteration results from a G to A substitution at nucleotide position 226, causing the glycine (G) at amino acid position 76 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
Cadd
Pathogenic
28
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.52
D;D;T;D
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.64
D;D;D;D
MetaSVM
Benign
-0.70
T
MutationAssessor
Pathogenic
3.9
H;H;.;H
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Pathogenic
-5.2
D;D;D;D
REVEL
Uncertain
0.41
Sift
Uncertain
0.0060
D;D;D;D
Sift4G
Uncertain
0.012
D;D;D;D
Polyphen
0.31
B;B;.;B
Vest4
0.63
MutPred
0.37
Gain of phosphorylation at G76 (P = 0.0149);Gain of phosphorylation at G76 (P = 0.0149);Gain of phosphorylation at G76 (P = 0.0149);Gain of phosphorylation at G76 (P = 0.0149);
MVP
0.52
MPC
0.65
ClinPred
1.0
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.96
gMVP
0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1026121520; hg19: chr2-55462003; API