1-213070988-A-C

Position:

• chr1-213070988-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_012424.6(RPS6KC1):​c.106-18A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,465,126 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (9 hom.)
• Consequence: RPS6KC1 NM_012424.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 1-213070988-A-C is Benign according to our data. Variant chr1-213070988-A-C is described in ClinVar as [Benign]. Clinvar id is 1618446.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KC1	NM_012424.6	c.106-18A>C		intron_variant		ENST00000366960.8	NP_036556.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KC1	ENST00000366960.8	c.106-18A>C		intron_variant		1	NM_012424.6	ENSP00000355927	P1

Frequencies

GnomAD3 genomes AF: 0.00132 AC: 201 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00131 AC: 281 AN: 214446 Hom.: 0 AF XY: 0.00136 AC XY: 159 AN XY: 116662

Gnomad AFR exome AF: 0.000996

Gnomad AMR exome AF: 0.00160

Gnomad ASJ exome AF: 0.000218

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000239

Gnomad NFE exome AF: 0.00211

Gnomad OTH exome AF: 0.00118

GnomAD4 exome AF: 0.00187 AC: 2451 AN: 1312798 Hom.: 9 Cov.: 19 AF XY: 0.00178 AC XY: 1174 AN XY: 658822

Gnomad4 AFR exome AF: 0.000381

Gnomad4 AMR exome AF: 0.00198

Gnomad4 ASJ exome AF: 0.000407

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000264

Gnomad4 FIN exome AF: 0.000323

Gnomad4 NFE exome AF: 0.00225

Gnomad4 OTH exome AF: 0.00165

GnomAD4 genome AF: 0.00132 AC: 201 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.00103 AC XY: 77 AN XY: 74492

Gnomad4 AFR AF: 0.000721

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00190

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.000504 Hom.: 0

Bravo AF: 0.00179

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.5
DANN	Benign	0.84

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

LitVar

Other links and lift over

dbSNP: rs79466500; hg19: chr1-213244330;