1-213071037-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012424.6(RPS6KC1):​c.137A>G​(p.Gln46Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,385,070 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: not found (cov: 32)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

RPS6KC1
NM_012424.6 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.95
Variant links:
Genes affected
RPS6KC1 (HGNC:10439): (ribosomal protein S6 kinase C1) Sphingosine kinase catalyzes the formation of sphingosine 1 phosphate, a lipid cellular messenger. The protein encoded by this gene can bind to sphingosine kinase and to phosphatidylinositol 3-phosphate, suggesting a role in sphingosine 1 phophate signaling. The encoded protein can also bind to peroxiredoxin-3 and may help transport it to mitochondria. [provided by RefSeq, Mar 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36061525).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPS6KC1NM_012424.6 linkc.137A>G p.Gln46Arg missense_variant Exon 2 of 15 ENST00000366960.8 NP_036556.2 Q96S38-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPS6KC1ENST00000366960.8 linkc.137A>G p.Gln46Arg missense_variant Exon 2 of 15 1 NM_012424.6 ENSP00000355927.3 Q96S38-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000918
AC:
2
AN:
217762
Hom.:
0
AF XY:
0.0000169
AC XY:
2
AN XY:
118400
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000380
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000654
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000217
AC:
3
AN:
1385070
Hom.:
0
Cov.:
22
AF XY:
0.00000289
AC XY:
2
AN XY:
691198
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000268
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000269
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.43e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000370
Hom.:
0
Bravo
AF:
0.00000378
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 provided Uncertain:1
Jun 16, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. 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. This variant has not been reported in the literature in individuals affected with RPS6KC1-related conditions. This variant is present in population databases (rs775834541, gnomAD 0.007%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 46 of the RPS6KC1 protein (p.Gln46Arg). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.36
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.36
T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
0.19
N
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.24
Sift
Benign
0.064
T
Sift4G
Uncertain
0.049
D
Polyphen
1.0
D
Vest4
0.49
MVP
0.52
MPC
0.15
ClinPred
0.58
D
GERP RS
5.4
Varity_R
0.30
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs775834541; hg19: chr1-213244379; API