1-213070988-A-G

Variant names:

• chr1-213070988-A-G
• rs79466500
• NM_012424.6:c.106-18A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_012424.6(RPS6KC1):​c.106-18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,465,194 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: RPS6KC1 NM_012424.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 1-213070988-A-G is Benign according to our data. Variant chr1-213070988-A-G is described in ClinVar as Benign. ClinVar VariationId is 1623900.Status of the report is criteria_provided_single_submitter, 1 stars.

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.106-18A>G		intron	N/A	NP_036556.2
	RPS6KC1	NM_001136138.4		c.106-6708A>G		intron	N/A	NP_001129610.1
	RPS6KC1	NM_001349646.2		c.106-18A>G		intron	N/A	NP_001336575.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KC1	ENST00000366960.8	TSL:1 MANE Select	c.106-18A>G		intron	N/A	ENSP00000355927.3
	RPS6KC1	ENST00000543354.5	TSL:1	c.-317-18A>G		intron	N/A	ENSP00000439282.2
	RPS6KC1	ENST00000614059.4	TSL:1	c.-516-18A>G		intron	N/A	ENSP00000483873.1

Frequencies

GnomAD3 genomes AF: 0.00152 AC: 231 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00444

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000457 AC: 98 AN: 214446 AF XY: 0.000411

Gnomad AFR exome AF: 0.00434

Gnomad AMR exome AF: 0.000821

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000139

Gnomad OTH exome AF: 0.000394

GnomAD4 exome AF: 0.000209 AC: 274 AN: 1312866 Hom.: 1 Cov.: 19 AF XY: 0.000202 AC XY: 133 AN XY: 658856

African (AFR) AF: 0.00485 AC: 140 AN: 28888

American (AMR) AF: 0.00101 AC: 36 AN: 35812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24558

East Asian (EAS) AF: 0.0000271 AC: 1 AN: 36838

South Asian (SAS) AF: 0.0000264 AC: 2 AN: 75716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52656

Middle Eastern (MID) AF: 0.00167 AC: 9 AN: 5382

European-Non Finnish (NFE) AF: 0.0000651 AC: 65 AN: 997964

Other (OTH) AF: 0.000381 AC: 21 AN: 55052

GnomAD4 genome AF: 0.00155 AC: 236 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.00153 AC XY: 114 AN XY: 74492

African (AFR) AF: 0.00454 AC: 189 AN: 41586

American (AMR) AF: 0.00183 AC: 28 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000720 Hom.: 0

Bravo AF: 0.00171

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.6
DANN	Benign	0.82
PhyloP100		-1.1

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: rs79466500; hg19: chr1-213244330;