1-213051480-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_012424.6(RPS6KC1):āc.76G>Cā(p.Gly26Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,612,964 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
RPS6KC1
NM_012424.6 missense
NM_012424.6 missense
Scores
10
3
6
Clinical Significance
Conservation
PhyloP100: 6.12
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RPS6KC1 | NM_012424.6 | c.76G>C | p.Gly26Arg | missense_variant | 1/15 | ENST00000366960.8 | NP_036556.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RPS6KC1 | ENST00000366960.8 | c.76G>C | p.Gly26Arg | missense_variant | 1/15 | 1 | NM_012424.6 | ENSP00000355927 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151788Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000244 AC: 6AN: 246116Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 133738
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461176Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726872
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GnomAD4 genome AF: 0.00000659 AC: 1AN: 151788Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74122
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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 | Mar 07, 2024 | The c.76G>C (p.G26R) alteration is located in exon 1 (coding exon 1) of the RPS6KC1 gene. This alteration results from a G to C substitution at nucleotide position 76, causing the glycine (G) at amino acid position 26 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0148);Gain of MoRF binding (P = 0.0148);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at