chr1-213051423-C-T

Variant names:

• chr1-213051423-C-T
• NM_012424.6:c.19C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012424.6(RPS6KC1):​c.19C>T​(p.Arg7Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: not found (cov: 32)
• Consequence: RPS6KC1 NM_012424.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.584
• Publications: 0 publications found

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]

RPS6KC1 Gene-Disease associations (from GenCC):

• periventricular leukomalacia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16914964).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012424.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KC1	NM_012424.6	MANE Select	c.19C>T	p.Arg7Trp	missense	Exon 1 of 15	NP_036556.2
	RPS6KC1	NM_001136138.4		c.19C>T	p.Arg7Trp	missense	Exon 1 of 14	NP_001129610.1	Q96S38-2
	RPS6KC1	NM_001349646.2		c.19C>T	p.Arg7Trp	missense	Exon 1 of 14	NP_001336575.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KC1	ENST00000366960.8	TSL:1 MANE Select	c.19C>T	p.Arg7Trp	missense	Exon 1 of 15	ENSP00000355927.3	Q96S38-1
	RPS6KC1	ENST00000543354.5	TSL:1	c.-404C>T		5_prime_UTR	Exon 1 of 14	ENSP00000439282.2	F6RJM5
	RPS6KC1	ENST00000614059.4	TSL:1	c.-603C>T		5_prime_UTR	Exon 1 of 15	ENSP00000483873.1	F5H7T0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.58
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.20
MutPred		0.32		Loss of disorder (P = 0.0022)
MVP		0.57
MPC		0.072
ClinPred		0.94	D
GERP RS		5.7
PromoterAI		0.00020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.35
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

hg19: chr1-213224765;