1-44778048-C-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001012.2(RPS8):​c.436C>G​(p.Gln146Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

RPS8
NM_001012.2 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.38
Variant links:
Genes affected
RPS8 (HGNC:10441): (ribosomal protein S8) 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 S8E family of ribosomal proteins. It is located in the cytoplasm. Increased expression of this gene in colorectal tumors and colon polyps compared to matched normal colonic mucosa has been observed. This gene is co-transcribed with the small nucleolar RNA genes U38A, U38B, U39, and U40, which are located in its fourth, fifth, first, and second introns, respectively. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]
SNORD38A (HGNC:30355): (small nucleolar RNA, C/D box 38A)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.31371588).
BS2
High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPS8NM_001012.2 linkc.436C>G p.Gln146Glu missense_variant Exon 5 of 6 ENST00000396651.8 NP_001003.1 P62241Q5JR94
SNORD38ANR_001456.1 linkn.*136C>G downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPS8ENST00000396651.8 linkc.436C>G p.Gln146Glu missense_variant Exon 5 of 6 1 NM_001012.2 ENSP00000379888.3 P62241

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152150
Hom.:
0
Cov.:
33
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
AF:
0.0000151
AC:
22
AN:
1461040
Hom.:
0
Cov.:
31
AF XY:
0.0000206
AC XY:
15
AN XY:
726790
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:
0.0000198
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152150
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74322
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
Feb 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.436C>G (p.Q146E) alteration is located in exon 5 (coding exon 5) of the RPS8 gene. This alteration results from a C to G substitution at nucleotide position 436, causing the glutamine (Q) at amino acid position 146 to be replaced by a glutamic acid (E). 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
0.21
BayesDel_addAF
Benign
-0.094
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
23
DANN
Benign
0.90
DEOGEN2
Benign
0.10
T;T
Eigen
Benign
-0.18
Eigen_PC
Benign
0.067
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.75
T;T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.18
N;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.22
Sift
Benign
0.69
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;.
Vest4
0.59
MutPred
0.44
Loss of helix (P = 0.079);.;
MVP
0.55
MPC
1.3
ClinPred
0.53
D
GERP RS
4.9
Varity_R
0.79
gMVP
0.69

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: rs757163051; hg19: chr1-45243720; API