Genetic Variant RPS6KC1:c.106-18A>C (chr1-213070988-A-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.05

Publications

0 publications found

Variant links:

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

RPS6KC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1618446.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RPS6KC1	NM_012424.6	MANE Select	c.106-18A>C	intron	N/A	NP_036556.2
RPS6KC1	NM_001136138.4		c.106-6708A>C	intron	N/A	NP_001129610.1
RPS6KC1	NM_001349646.2		c.106-18A>C	intron	N/A	NP_001336575.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

201

AN:

152210

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00131

AC:

281

AN:

214446

AF XY:

0.00136

show subpopulations

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 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.:

Cov.:

AF XY:

0.00178

AC XY:

1174

AN XY:

658822

show subpopulations

African (AFR)

AF:

0.000381

AC:

AN:

28890

American (AMR)

AF:

0.00198

AC:

AN:

35810

Ashkenazi Jewish (ASJ)

AF:

0.000407

AC:

AN:

24558

East Asian (EAS)

AF:

0.00

AC:

AN:

36838

South Asian (SAS)

AF:

0.0000264

AC:

AN:

75716

European-Finnish (FIN)

AF:

0.000323

AC:

AN:

52656

Middle Eastern (MID)

AF:

0.000186

AC:

AN:

5382

European-Non Finnish (NFE)

AF:

0.00225

AC:

2248

AN:

997898

Other (OTH)

AF:

0.00165

AC:

AN:

55050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

104

208

312

416

520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00132

AC:

201

AN:

152328

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.000721

AC:

AN:

41586

American (AMR)

AF:

0.00170

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00190

AC:

129

AN:

68012

Other (OTH)

AF:

0.00521

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000504

Hom.:

Bravo

AF:

0.00179

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.5

(source)

DANN

Benign

0.84

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over