5-97167726-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_018343.3(RIOK2):ā€‹c.1138A>Gā€‹(p.Ser380Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,614,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000010 ( 0 hom. )

Consequence

RIOK2
NM_018343.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.903
Variant links:
Genes affected
RIOK2 (HGNC:18999): (RIO kinase 2) Predicted to enable protein kinase activity. Involved in several processes, including positive regulation of rRNA processing; positive regulation of ribosomal small subunit export from nucleus; and regulation of mitotic metaphase/anaphase transition. Located in cytoplasm. Part of preribosome, small subunit precursor. [provided by Alliance of Genome Resources, Apr 2022]
LIX1-AS1 (HGNC:52976): (LIX1 and RIOK2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity RIOK2_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.020432651).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RIOK2NM_018343.3 linkc.1138A>G p.Ser380Gly missense_variant 8/10 ENST00000283109.8 NP_060813.2 Q9BVS4-1
RIOK2NM_001159749.2 linkc.1138A>G p.Ser380Gly missense_variant 8/8 NP_001153221.1 Q9BVS4-2
RIOK2XM_017009628.2 linkc.577A>G p.Ser193Gly missense_variant 6/8 XP_016865117.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RIOK2ENST00000283109.8 linkc.1138A>G p.Ser380Gly missense_variant 8/101 NM_018343.3 ENSP00000283109.3 Q9BVS4-1
RIOK2ENST00000508447.1 linkc.1138A>G p.Ser380Gly missense_variant 8/81 ENSP00000420932.1 Q9BVS4-2
LIX1-AS1ENST00000504578.2 linkn.574-15282T>C intron_variant 5
RIOK2ENST00000511012.1 linkc.-9A>G upstream_gene_variant 2 ENSP00000422772.1 H0Y919

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152264
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:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251028
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135662
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:
0.000185
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461818
Hom.:
0
Cov.:
32
AF XY:
0.00000963
AC XY:
7
AN XY:
727210
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:
0.000243
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152382
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74524
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:
0.0000941
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

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 GeneticsAug 05, 2024The c.1138A>G (p.S380G) alteration is located in exon 8 (coding exon 8) of the RIOK2 gene. This alteration results from a A to G substitution at nucleotide position 1138, causing the serine (S) at amino acid position 380 to be replaced by a glycine (G). 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
0.061
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.019
DANN
Benign
0.61
DEOGEN2
Benign
0.0044
T;.
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.42
T;T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.020
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.98
L;L
PrimateAI
Benign
0.18
T
PROVEAN
Benign
-0.030
N;N
REVEL
Benign
0.096
Sift
Benign
0.47
T;T
Sift4G
Benign
0.36
T;T
Polyphen
0.0
B;.
Vest4
0.046
MVP
0.16
MPC
0.13
ClinPred
0.023
T
GERP RS
-10
Varity_R
0.018
gMVP
0.089

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: rs191630960; hg19: chr5-96503430; API