chrX-20155127-A-G

Position:

• chrX-20155127-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004586.3(RPS6KA3):​c.*271T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 363,493 control chromosomes in the GnomAD database, including 125 homozygotes. There are 954 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (96 hom., 752 hem., cov: 23)
  • Exomes 𝑓: 0.0034 (29 hom. 202 hem.)
• Consequence: RPS6KA3 NM_004586.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.582

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant X-20155127-A-G is Benign according to our data. Variant chrX-20155127-A-G is described in ClinVar as [Benign]. Clinvar id is 1248010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA3	NM_004586.3	c.*271T>C		3_prime_UTR_variant	22/22	ENST00000379565.9	NP_004577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA3	ENST00000379565	c.*271T>C		3_prime_UTR_variant	22/22	1	NM_004586.3	ENSP00000368884.3

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 2771 AN: 112070 Hom.: 96 Cov.: 23 AF XY: 0.0214 AC XY: 732 AN XY: 34240

Gnomad AFR AF: 0.0861

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00828

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.000188

Gnomad OTH AF: 0.0159

GnomAD4 exome AF: 0.00343 AC: 862 AN: 251371 Hom.: 29 Cov.: 0 AF XY: 0.00263 AC XY: 202 AN XY: 76761

Gnomad4 AFR exome AF: 0.0836

Gnomad4 AMR exome AF: 0.00487

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000194

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000145

Gnomad4 OTH exome AF: 0.00792

GnomAD4 genome AF: 0.0249 AC: 2793 AN: 112122 Hom.: 96 Cov.: 23 AF XY: 0.0219 AC XY: 752 AN XY: 34302

Gnomad4 AFR AF: 0.0866

Gnomad4 AMR AF: 0.00827

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000188

Gnomad4 OTH AF: 0.0157

Alfa AF: 0.0113 Hom.: 61

Bravo AF: 0.0282

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	GeneDx	Nov 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	10
DANN	Benign	0.86

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: rs112566025; hg19: chrX-20173245;