rs10494962

Variant names:

• chr1-213727915-A-G
• rs10494962
• ENST00000788945.1:n.297-3502A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000788945.1(ENSG00000225233):​n.297-3502A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,056 control chromosomes in the GnomAD database, including 6,913 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6913 hom., cov: 32)
• Consequence: ENSG00000225233 ENST00000788945.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 2 publications found

Genes affected

ENSG00000225233 (HGNC:):

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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000788945.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000225233	ENST00000788945.1		n.297-3502A>G		intron	N/A
	ENSG00000225233	ENST00000788946.1		n.302-3502A>G		intron	N/A
	ENSG00000225233	ENST00000788947.1		n.457-3502A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42978 AN: 151938 Hom.: 6905 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0580

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.271

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.283 AC: 43006 AN: 152056 Hom.: 6913 Cov.: 32 AF XY: 0.278 AC XY: 20639 AN XY: 74352

African (AFR) AF: 0.424 AC: 17579 AN: 41450

American (AMR) AF: 0.196 AC: 2987 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 897 AN: 3470

East Asian (EAS) AF: 0.0578 AC: 299 AN: 5176

South Asian (SAS) AF: 0.294 AC: 1413 AN: 4808

European-Finnish (FIN) AF: 0.161 AC: 1706 AN: 10582

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17059 AN: 67978

Other (OTH) AF: 0.272 AC: 573 AN: 2110

Alfa AF: 0.257 Hom.: 940

Bravo AF: 0.293

Asia WGS AF: 0.213 AC: 741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10494962; hg19: chr1-213901258;