rs1357449306

Variant names:

• chr1-213051424-G-A
• NM_012424.6:c.20G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-213051424-G-A
• chr1-213051424-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012424.6(RPS6KC1):​c.20G>A​(p.Arg7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7L) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: RPS6KC1 NM_012424.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08240992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KC1	NM_012424.6	c.20G>A	p.Arg7Gln	missense_variant	Exon 1 of 15	ENST00000366960.8	NP_036556.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KC1	ENST00000366960.8	c.20G>A	p.Arg7Gln	missense_variant	Exon 1 of 15	1	NM_012424.6	ENSP00000355927.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74462

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.97	N;N
REVEL	Benign	0.031
Sift	Benign	0.10	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.11	B;.
Vest4		0.13
MutPred		0.17		Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);
MVP		0.33
MPC		0.079
ClinPred		0.35	T
GERP RS		0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.057
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-213224766;