11-64360272-A-G

Position:

• chr11-64360272-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_003942.3(RPS6KA4):​c.237A>G​(p.Gln79=) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.316

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]

ACMG classification

Verdict is Benign. Variant got -15 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_single_submitter, 1 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/exons	MANE	UniProt
RPS6KA4	NM_003942.3	c.237A>G	p.Gln79=	synonymous_variant	3/17	ENST00000334205.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA4	ENST00000334205.9	c.237A>G	p.Gln79=	synonymous_variant	3/17	1	NM_003942.3	P1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51169 AN: 152052 Hom.: 10357 Cov.: 33

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

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.: 62 AF XY: 0.426 AC XY: 293086 AN XY: 688202

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.: 33 AF XY: 0.340 AC XY: 25287 AN XY: 74404

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
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

Other links and lift over

dbSNP: rs521950; hg19: chr11-64127744; COSMIC: COSV53701593; COSMIC: COSV53701593;