Variant X-84135175-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_014496.5(RPS6KA6):c.537C>T(p.Leu179=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000864 in 1,201,025 control chromosomes in the GnomAD database, including 2 homozygotes. There are 347 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00092 ( 0 hom., 32 hem., cov: 23)

Exomes 𝑓: 0.00086 ( 2 hom. 315 hem. )

Consequence

RPS6KA6
NM_014496.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.269

Variant links:

Genes affected

RPS6KA6 (HGNC:10435): (ribosomal protein S6 kinase A6) This gene encodes a member of ribosomal S6 kinase family, serine-threonine protein kinases which are regulated by growth factors. The encoded protein may be distinct from other members of this family, however, as studies suggest it is not growth factor dependent and may not participate in the same signaling pathways. [provided by RefSeq, Jan 2010]

RPS6KA6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant X-84135175-G-A is Benign according to our data. Variant chrX-84135175-G-A is described in ClinVar as [Benign]. Clinvar id is 723331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-84135175-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.269 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA6	NM_014496.5 linkuse as main transcript	c.537C>T	p.Leu179=	synonymous_variant	7/22	ENST00000262752.5	NP_055311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA6	ENST00000262752.5 linkuse as main transcript	c.537C>T	p.Leu179=	synonymous_variant	7/22	1	NM_014496.5	ENSP00000262752	P1	Q9UK32-1
RPS6KA6	ENST00000620340.4 linkuse as main transcript	c.537C>T	p.Leu179=	synonymous_variant	7/22	5		ENSP00000483896		Q9UK32-2

Frequencies

GnomAD3 genomes

AF:

0.000923

AC:

103

AN:

111542

Hom.:

Cov.:

AF XY:

0.000947

AC XY:

AN XY:

33800

show subpopulations

Gnomad AFR

AF:

0.000195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000478

Gnomad ASJ

AF:

0.000756

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000744

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00424

Gnomad NFE

AF:

0.00164

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000757

AC:

134

AN:

177018

Hom.:

AF XY:

0.000900

AC XY:

AN XY:

62240

show subpopulations

Gnomad AFR exome

AF:

0.000310

Gnomad AMR exome

AF:

0.000672

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000280

Gnomad FIN exome

AF:

0.0000633

Gnomad NFE exome

AF:

0.00119

Gnomad OTH exome

AF:

0.00297

GnomAD4 exome

AF:

0.000858

AC:

935

AN:

1089431

Hom.:

Cov.:

AF XY:

0.000885

AC XY:

315

AN XY:

355917

show subpopulations

Gnomad4 AFR exome

AF:

0.000153

Gnomad4 AMR exome

AF:

0.000572

Gnomad4 ASJ exome

AF:

0.000156

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000319

Gnomad4 FIN exome

AF:

0.000371

Gnomad4 NFE exome

AF:

0.000966

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.000923

AC:

103

AN:

111594

Hom.:

Cov.:

AF XY:

0.000945

AC XY:

AN XY:

33862

show subpopulations

Gnomad4 AFR

AF:

0.000194

Gnomad4 AMR

AF:

0.000478

Gnomad4 ASJ

AF:

0.000756

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000746

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00164

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00120

Hom.:

Bravo

AF:

0.000854

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	Aug 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.34

DANN

Benign

0.78

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

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