Genetic Variant RPS6KA1:c.*398C>T (chr1-26574599-C-T) – 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.*398C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 389,256 control chromosomes in the GnomAD database, including 70,859 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 0.61 ( 28100 hom., cov: 30)

Exomes 𝑓: 0.60 ( 42759 hom. )

Consequence

RPS6KA1
NM_002953.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.548

Publications

15 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:

Genome browser will be placed here

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=-0.53).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA1	NM_002953.4 link	c.*398C>T	3_prime_UTR_variant	Exon 22 of 22	ENST00000374168.7	NP_002944.2	Q15418-1
RPS6KA1	NM_001006665.2 link	c.*398C>T	3_prime_UTR_variant	Exon 21 of 21		NP_001006666.1	Q15418-2
RPS6KA1	NM_001330441.2 link	c.*398C>T	3_prime_UTR_variant	Exon 21 of 21		NP_001317370.1	Q15418-4
RPS6KA1	XM_024448871.2 link	c.*398C>T	3_prime_UTR_variant	Exon 22 of 22		XP_024304639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA1	ENST00000374168.7 link	c.*398C>T		3_prime_UTR_variant	Exon 22 of 22	1	NM_002953.4	ENSP00000363283.2		Q15418-1

Frequencies

GnomAD3 genomes

AF:

0.606

AC:

91968

AN:

151706

Hom.:

28086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.674

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.531

Gnomad EAS

AF:

0.712

Gnomad SAS

AF:

0.664

Gnomad FIN

AF:

0.566

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.595

GnomAD4 exome

AF:

0.596

AC:

141438

AN:

237432

Hom.:

42759

Cov.:

AF XY:

0.600

AC XY:

79780

AN XY:

132988

show subpopulations

African (AFR)

AF:

0.681

AC:

4305

AN:

6326

American (AMR)

AF:

0.612

AC:

10358

AN:

16938

Ashkenazi Jewish (ASJ)

AF:

0.538

AC:

3188

AN:

5928

East Asian (EAS)

AF:

0.722

AC:

6537

AN:

9054

South Asian (SAS)

AF:

0.646

AC:

30317

AN:

46960

European-Finnish (FIN)

AF:

0.567

AC:

5633

AN:

9940

Middle Eastern (MID)

AF:

0.602

AC:

920

AN:

1528

European-Non Finnish (NFE)

AF:

0.568

AC:

73497

AN:

129460

Other (OTH)

AF:

0.592

AC:

6683

AN:

11298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

3236

6472

9708

12944

16180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

516

1032

1548

2064

2580

<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:

0.606

AC:

92030

AN:

151824

Hom.:

28100

Cov.:

AF XY:

0.605

AC XY:

44872

AN XY:

74162

show subpopulations

African (AFR)

AF:

0.673

AC:

27898

AN:

41430

American (AMR)

AF:

0.598

AC:

9116

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

1840

AN:

3468

East Asian (EAS)

AF:

0.712

AC:

3665

AN:

5146

South Asian (SAS)

AF:

0.664

AC:

3183

AN:

4794

European-Finnish (FIN)

AF:

0.566

AC:

5971

AN:

10546

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.567

AC:

38482

AN:

67890

Other (OTH)

AF:

0.596

AC:

1257

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1821

3642

5464

7285

9106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

768

1536

2304

3072

3840

<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:

0.583

Hom.:

45192

Bravo

AF:

0.614

Asia WGS

AF:

0.657

AC:

2287

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

3.0

(source)

DANN

Benign

0.87

PhyloP100

-0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over