1-153991142-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001030.6(RPS27):​c.34C>T​(p.Pro12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RPS27
NM_001030.6 missense

Scores

5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26
Variant links:
Genes affected
RPS27 (HGNC:10416): (ribosomal protein S27) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the S27e family of ribosomal proteins and component of the 40S subunit. The encoded protein contains a C4-type zinc finger domain that can bind to zinc and may bind to nucleic acid. Mutations in this gene have been identified in numerous melanoma patients and in at least one patient with Diamond-Blackfan anemia (DBA). Elevated expression of this gene has been observed in various human cancers. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2018]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16349915).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPS27NM_001030.6 linkc.34C>T p.Pro12Ser missense_variant Exon 2 of 4 ENST00000651669.1 NP_001021.1 P42677
RPS27NM_001349946.2 linkc.-63C>T 5_prime_UTR_variant Exon 3 of 5 NP_001336875.1
RPS27NM_001349947.2 linkc.-63C>T 5_prime_UTR_variant Exon 2 of 4 NP_001336876.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPS27ENST00000651669.1 linkc.34C>T p.Pro12Ser missense_variant Exon 2 of 4 NM_001030.6 ENSP00000499044.1 P42677

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000139
AC:
2
AN:
1442974
Hom.:
0
Cov.:
31
AF XY:
0.00000140
AC XY:
1
AN XY:
716476
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:
0.00000182
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
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
Jan 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.34C>T (p.P12S) alteration is located in exon 2 (coding exon 2) of the RPS27 gene. This alteration results from a C to T substitution at nucleotide position 34, causing the proline (P) at amino acid position 12 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
Benign
0.20
BayesDel_addAF
Uncertain
0.034
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T
Eigen
Benign
-0.13
Eigen_PC
Benign
0.0022
FATHMM_MKL
Benign
0.24
N
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.0093
T
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-3.7
D
REVEL
Benign
0.20
Sift
Benign
0.055
T
Sift4G
Benign
0.29
T
Polyphen
0.0
B
Vest4
0.31
MutPred
0.18
Gain of phosphorylation at P12 (P = 0.0031);
MVP
0.37
MPC
0.76
ClinPred
0.94
D
GERP RS
5.1
Varity_R
0.54
gMVP
0.18

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: rs1333360079; hg19: chr1-153963618; API