Genetic Variant RPS6KA4:p.Gln79Gln (chr11-64360272-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003942.3(RPS6KA4):c.237A>G(p.Gln79Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,547,596 control chromosomes in the GnomAD database, including 141,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 10354 hom., cov: 33)

Exomes 𝑓: 0.43 ( 130801 hom. )

Consequence

RPS6KA4
NM_003942.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.316

Variant links:

Genes affected

RPS6KA4 (HGNC:10433): (ribosomal protein S6 kinase A4) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 non-identical kinase catalytic domains and phosphorylates various substrates, including CREB1 and ATF1. The encoded protein can also phosphorylate histone H3 to regulate certain inflammatory genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

RPS6KA4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 11-64360272-A-G is Benign according to our data. Variant chr11-64360272-A-G is described in ClinVar as [Benign]. Clinvar id is 1227675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.316 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA4	NM_003942.3 link	c.237A>G	p.Gln79Gln	synonymous_variant	Exon 3 of 17	ENST00000334205.9	NP_003933.1	O75676-1A0PJF8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA4	ENST00000334205.9 link	c.237A>G	p.Gln79Gln	synonymous_variant	Exon 3 of 17	1	NM_003942.3	ENSP00000333896.4		O75676-1

Frequencies

GnomAD3 genomes

AF:

0.337

AC:

51169

AN:

152052

Hom.:

10357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.421

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.319

GnomAD3 exomes

AF:

0.388

AC:

58406

AN:

150340

Hom.:

12203

AF XY:

0.390

AC XY:

31212

AN XY:

80066

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.395

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.209

Gnomad SAS exome

AF:

0.382

Gnomad FIN exome

AF:

0.480

Gnomad NFE exome

AF:

0.436

Gnomad OTH exome

AF:

0.374

GnomAD4 exome

AF:

0.427

AC:

595761

AN:

1395426

Hom.:

130801

Cov.:

AF XY:

0.426

AC XY:

293086

AN XY:

688202

show subpopulations

Gnomad4 AFR exome

AF:

0.0978

Gnomad4 AMR exome

AF:

0.398

Gnomad4 ASJ exome

AF:

0.411

Gnomad4 EAS exome

AF:

0.237

Gnomad4 SAS exome

AF:

0.387

Gnomad4 FIN exome

AF:

0.478

Gnomad4 NFE exome

AF:

0.448

Gnomad4 OTH exome

AF:

0.383

GnomAD4 genome

AF:

0.336

AC:

51175

AN:

152170

Hom.:

10354

Cov.:

AF XY:

0.340

AC XY:

25287

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.112

Gnomad4 AMR

AF:

0.379

Gnomad4 ASJ

AF:

0.421

Gnomad4 EAS

AF:

0.222

Gnomad4 SAS

AF:

0.399

Gnomad4 FIN

AF:

0.471

Gnomad4 NFE

AF:

0.443

Gnomad4 OTH

AF:

0.315

Alfa

AF:

0.415

Hom.:

4864

Bravo

AF:

0.317

Asia WGS

AF:

0.320

AC:

1114

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.37

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