Variant 17-59914627-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000225577.9(RPS6KB1):c.313-8T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00915 in 1,610,504 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0093 ( 76 hom. )

Consequence

RPS6KB1
ENST00000225577.9 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.3328

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.28

Variant links:

Genes affected

RPS6KB1 (HGNC:10436): (ribosomal protein S6 kinase B1) This gene encodes a member of the ribosomal S6 kinase family of serine/threonine kinases. The encoded protein responds to mTOR (mammalian target of rapamycin) signaling to promote protein synthesis, cell growth, and cell proliferation. Activity of this gene has been associated with human cancer. Alternatively spliced transcript variants have been observed. The use of alternative translation start sites results in isoforms with longer or shorter N-termini which may differ in their subcellular localizations. There are two pseudogenes for this gene on chromosome 17. [provided by RefSeq, Jan 2013]

RPS6KB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 17-59914627-T-A is Benign according to our data. Variant chr17-59914627-T-A is described in ClinVar as [Benign]. Clinvar id is 778132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1111 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KB1	NM_003161.4 linkuse as main transcript	c.313-8T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000225577.9	NP_003152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KB1	ENST00000225577.9 linkuse as main transcript	c.313-8T>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003161.4	ENSP00000225577	A1	P23443-1

Frequencies

GnomAD3 genomes

AF:

0.00729

AC:

1110

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00725

AC:

1812

AN:

250094

Hom.:

AF XY:

0.00764

AC XY:

1032

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.00173

Gnomad AMR exome

AF:

0.00829

Gnomad ASJ exome

AF:

0.00686

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00302

Gnomad FIN exome

AF:

0.00106

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.0129

GnomAD4 exome

AF:

0.00934

AC:

13625

AN:

1458214

Hom.:

Cov.:

AF XY:

0.00912

AC XY:

6616

AN XY:

725534

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00846

Gnomad4 ASJ exome

AF:

0.00640

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00327

Gnomad4 FIN exome

AF:

0.00178

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.00834

GnomAD4 genome

AF:

0.00730

AC:

1111

AN:

152290

Hom.:

Cov.:

AF XY:

0.00692

AC XY:

515

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00224

Gnomad4 AMR

AF:

0.0115

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.0113

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00830

Hom.:

Bravo

AF:

0.00790

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0130

EpiControl

AF:

0.0128

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.33

dbscSNV1_RF

Benign

0.32

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over