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GeneBe

2-55234124-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_002954.6(RPS27A):c.109C>A(p.Pro37Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,460,440 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RPS27A
NM_002954.6 missense

Scores

7
10
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86
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 Likely_benign. Variant got -2 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.842
BS2
High AC in GnomAdExome at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS27ANM_002954.6 linkuse as main transcriptc.109C>A p.Pro37Thr missense_variant 4/6 ENST00000272317.11
RPS27ANM_001135592.2 linkuse as main transcriptc.109C>A p.Pro37Thr missense_variant 4/6
RPS27ANM_001177413.1 linkuse as main transcriptc.109C>A p.Pro37Thr missense_variant 3/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS27AENST00000272317.11 linkuse as main transcriptc.109C>A p.Pro37Thr missense_variant 4/61 NM_002954.6 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251144
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135730
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000793
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1460440
Hom.:
0
Cov.:
29
AF XY:
0.00000826
AC XY:
6
AN XY:
726626
show subpopulations
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:
0.0000135
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 31, 2023The c.109C>A (p.P37T) alteration is located in exon 4 (coding exon 3) of the RPS27A gene. This alteration results from a C to A substitution at nucleotide position 109, causing the proline (P) at amino acid position 37 to be replaced by a threonine (T). 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
0.99
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Uncertain
0.090
Cadd
Pathogenic
29
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.48
T;T;T;T;T
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.98
D
M_CAP
Uncertain
0.25
D
MetaRNN
Pathogenic
0.84
D;D;D;D;D
MetaSVM
Uncertain
0.34
D
MutationAssessor
Uncertain
2.9
M;M;.;.;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.90
D
PROVEAN
Pathogenic
-7.5
D;D;.;D;D
REVEL
Pathogenic
0.74
Sift
Uncertain
0.0010
D;D;.;D;D
Sift4G
Pathogenic
0.0010
D;D;.;D;D
Polyphen
0.62
P;P;.;.;P
Vest4
0.86
MutPred
0.60
Loss of catalytic residue at P37 (P = 0.0077);Loss of catalytic residue at P37 (P = 0.0077);Loss of catalytic residue at P37 (P = 0.0077);Loss of catalytic residue at P37 (P = 0.0077);Loss of catalytic residue at P37 (P = 0.0077);
MVP
0.77
MPC
1.6
ClinPred
0.97
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.94
gMVP
0.61

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: rs779482327; hg19: chr2-55461260; API