Variant 1-153991595-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001030.6(RPS27):c.145C>T(p.His49Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,762 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: 6.8e-7 ( 0 hom. )

Consequence

RPS27
NM_001030.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.02

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]

RPS27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RPS27	NM_001030.6 linkuse as main transcript	c.145C>T	p.His49Tyr	missense_variant	3/4	ENST00000651669.1	NP_001021.1
RPS27	NM_001349946.2 linkuse as main transcript	c.49C>T	p.His17Tyr	missense_variant	4/5		NP_001336875.1
RPS27	NM_001349947.2 linkuse as main transcript	c.49C>T	p.His17Tyr	missense_variant	3/4		NP_001336876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS27	ENST00000651669.1 linkuse as main transcript	c.145C>T	p.His49Tyr	missense_variant	3/4		NM_001030.6	ENSP00000499044	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460762

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726764

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 15, 2023

This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 49 of the RPS27 protein (p.His49Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RPS27-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

M_CAP

Benign

0.056

MetaRNN

Pathogenic

0.83

MetaSVM

Benign

-0.73

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-5.9

REVEL

Uncertain

0.30

Sift

Benign

0.038

Sift4G

Uncertain

0.035

Polyphen

0.019

Vest4

0.75

MutPred

0.76

Gain of sheet (P = 0.0827);

MVP

0.58

MPC

0.88

ClinPred

0.99

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.83

gMVP

0.49

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over