Genetic Variant RPS6KA1:c.109-804A>G (chr1-26546063-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002953.4(RPS6KA1):c.109-804A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,606,354 control chromosomes in the GnomAD database, including 84,393 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 0.36 ( 10852 hom., cov: 33)

Exomes 𝑓: 0.30 ( 73541 hom. )

Consequence

RPS6KA1
NM_002953.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.131

Publications

8 publications found

Variant links:

Genes affected

RPS6KA1 (HGNC:10430): (ribosomal protein S6 kinase A1) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 nonidentical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

RPS6KA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002953.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS6KA1	NM_002953.4	MANE Select	c.109-804A>G	intron	N/A	NP_002944.2
RPS6KA1	NM_001006665.2		c.135+28A>G	intron	N/A	NP_001006666.1	Q15418-2
RPS6KA1	NM_001330441.2		c.61-804A>G	intron	N/A	NP_001317370.1	Q15418-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS6KA1	ENST00000374168.7	TSL:1 MANE Select	c.109-804A>G	intron	N/A	ENSP00000363283.2	Q15418-1
RPS6KA1	ENST00000531382.5	TSL:2	c.135+28A>G	intron	N/A	ENSP00000435412.1	Q15418-2
RPS6KA1	ENST00000952528.1		c.109-804A>G	intron	N/A	ENSP00000622587.1

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54379

AN:

151950

Hom.:

10849

Cov.:

show subpopulations

Gnomad AFR

AF:

0.475

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.366

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.765

Gnomad SAS

AF:

0.511

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.325

Gnomad NFE

AF:

0.259

Gnomad OTH

AF:

0.357

GnomAD2 exomes

AF:

0.372

AC:

86406

AN:

232264

AF XY:

0.368

show subpopulations

Gnomad AFR exome

AF:

0.474

Gnomad AMR exome

AF:

0.418

Gnomad ASJ exome

AF:

0.285

Gnomad EAS exome

AF:

0.771

Gnomad FIN exome

AF:

0.286

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.324

GnomAD4 exome

AF:

0.300

AC:

435670

AN:

1454284

Hom.:

73541

Cov.:

AF XY:

0.303

AC XY:

219223

AN XY:

723592

show subpopulations

African (AFR)

AF:

0.471

AC:

15504

AN:

32896

American (AMR)

AF:

0.407

AC:

17816

AN:

43770

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

7242

AN:

25906

East Asian (EAS)

AF:

0.752

AC:

29117

AN:

38720

South Asian (SAS)

AF:

0.478

AC:

40907

AN:

85596

European-Finnish (FIN)

AF:

0.293

AC:

15337

AN:

52424

Middle Eastern (MID)

AF:

0.303

AC:

1716

AN:

5670

European-Non Finnish (NFE)

AF:

0.260

AC:

288196

AN:

1109216

Other (OTH)

AF:

0.330

AC:

19835

AN:

60086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

15349

30697

46046

61394

76743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10118

20236

30354

40472

50590

<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:

0.358

AC:

54413

AN:

152070

Hom.:

10852

Cov.:

AF XY:

0.363

AC XY:

26982

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.475

AC:

19703

AN:

41482

American (AMR)

AF:

0.365

AC:

5586

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

967

AN:

3470

East Asian (EAS)

AF:

0.765

AC:

3936

AN:

5148

South Asian (SAS)

AF:

0.509

AC:

2455

AN:

4826

European-Finnish (FIN)

AF:

0.282

AC:

2991

AN:

10588

Middle Eastern (MID)

AF:

0.329

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.259

AC:

17594

AN:

67950

Other (OTH)

AF:

0.359

AC:

759

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1719

3438

5158

6877

8596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.282

Hom.:

1205

Bravo

AF:

0.369

Asia WGS

AF:

0.608

AC:

2109

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

-0.13

PromoterAI

0.044

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

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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