1-213244715-T-C

Variant names:

• chr1-213244715-T-C
• rs9308430
• NM_012424.6:c.2911+2057T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012424.6(RPS6KC1):​c.2911+2057T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,996 control chromosomes in the GnomAD database, including 6,371 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 0.27 (6371 hom., cov: 32)
• Consequence: RPS6KC1 NM_012424.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KC1	NM_012424.6	c.2911+2057T>C		intron_variant	Intron 12 of 14	ENST00000366960.8	NP_036556.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KC1	ENST00000366960.8	c.2911+2057T>C		intron_variant	Intron 12 of 14	1	NM_012424.6	ENSP00000355927.3

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40949 AN: 151878 Hom.: 6357 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.270 AC: 40989 AN: 151996 Hom.: 6371 Cov.: 32 AF XY: 0.272 AC XY: 20239 AN XY: 74296

African (AFR) AF: 0.123 AC: 5105 AN: 41480

American (AMR) AF: 0.400 AC: 6107 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1245 AN: 3472

East Asian (EAS) AF: 0.402 AC: 2077 AN: 5170

South Asian (SAS) AF: 0.328 AC: 1581 AN: 4816

European-Finnish (FIN) AF: 0.324 AC: 3423 AN: 10556

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20467 AN: 67924

Other (OTH) AF: 0.297 AC: 627 AN: 2110

Alfa AF: 0.284 Hom.: 1417

Bravo AF: 0.272

Asia WGS AF: 0.359 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.4
DANN	Benign	0.68
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs9308430; hg19: chr1-213418058;