5-150444296-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_005617.4(RPS14):c.446G>A(p.Arg149His) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,084 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPS14
NM_005617.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71

Variant links:

Genes affected

RPS14 (HGNC:10387): (ribosomal protein S14) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S11P family of ribosomal proteins. It is located in the cytoplasm. Transcript variants utilizing alternative transcription initiation sites have been described in the literature. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. In Chinese hamster ovary cells, mutations in this gene can lead to resistance to emetine, a protein synthesis inhibitor. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

RPS14 links:

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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;

PP2

Missense variant where missense usually causes diseases, RPS14

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RPS14	NM_005617.4 linkuse as main transcript	c.446G>A	p.Arg149His	missense_variant	5/5	ENST00000407193.7
RPS14	NM_001025070.2 linkuse as main transcript	c.446G>A	p.Arg149His	missense_variant	5/5
RPS14	NM_001025071.2 linkuse as main transcript	c.446G>A	p.Arg149His	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS14	ENST00000407193.7 linkuse as main transcript	c.446G>A	p.Arg149His	missense_variant	5/5	2	NM_005617.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152084

Hom.:

Cov.:

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: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1456660

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724310

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74276

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

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 submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.446G>A (p.R149H) alteration is located in exon 5 (coding exon 4) of the RPS14 gene. This alteration results from a G to A substitution at nucleotide position 446, causing the arginine (R) at amino acid position 149 to be replaced by a histidine (H). 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

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

Cadd

Pathogenic

Dann

Uncertain

0.98

DEOGEN2

Uncertain

0.56

D;D;D;D;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.081

MetaRNN

Uncertain

0.47

T;T;T;T;T

MetaSVM

Uncertain

-0.17

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.9

D;D;D;D;.

REVEL

Uncertain

0.40

Sift

Benign

0.19

T;T;T;T;.

Sift4G

Uncertain

0.019

D;D;D;D;.

Polyphen

0.98

D;D;D;D;.

Vest4

0.59

MutPred

0.29

Loss of methylation at R149 (P = 0.0148);Loss of methylation at R149 (P = 0.0148);Loss of methylation at R149 (P = 0.0148);Loss of methylation at R149 (P = 0.0148);Loss of methylation at R149 (P = 0.0148);

MVP

0.43

MPC

2.2

ClinPred

0.98

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.57

gMVP

0.76

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over