X-20155892-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004586.3(RPS6KA3):c.2100+217G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 112,305 control chromosomes in the GnomAD database, including 9 homozygotes. There are 439 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.013 (9 hom., 439 hem., cov: 22)
• Consequence: RPS6KA3 NM_004586.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0720

Genes affected

RPS6KA3 (HGNC:10432): (ribosomal protein S6 kinase A3) 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 members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Mutations in this gene have been associated with Coffin-Lowry syndrome (CLS). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant X-20155892-C-T is Benign according to our data. Variant chrX-20155892-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1193963.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA3	NM_004586.3	c.2100+217G>A		intron_variant		ENST00000379565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA3	ENST00000379565.9	c.2100+217G>A		intron_variant		1	NM_004586.3	P4

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1412 AN: 112254 Hom.: 9 Cov.: 22 AF XY: 0.0125 AC XY: 430 AN XY: 34424

Gnomad AFR AF: 0.00901

Gnomad AMI AF: 0.0533

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.0491

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00587

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.0167

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.0185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0127 AC: 1421 AN: 112305 Hom.: 9 Cov.: 22 AF XY: 0.0127 AC XY: 439 AN XY: 34485

Gnomad4 AFR AF: 0.00928

Gnomad4 AMR AF: 0.0153

Gnomad4 ASJ AF: 0.0491

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00626

Gnomad4 FIN AF: 0.00490

Gnomad4 NFE AF: 0.0137

Gnomad4 OTH AF: 0.0182

Alfa AF: 0.0122 Hom.: 56

Bravo AF: 0.0150

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.5
Dann	Benign	0.39

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: rs111948591; hg19: chrX-20174010;