rs1160828151

Variant names:

• chrX-20172791-G-A
• rs1160828151
• NM_004586.3:c.1308C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-20172791-G-A
• chrX-20172791-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_004586.3(RPS6KA3):​c.1308C>T​(p.Cys436Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000092 in 1,087,470 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: RPS6KA3 NM_004586.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 0 publications found

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]

RPS6KA3 Gene-Disease associations (from GenCC):

• Coffin-Lowry syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, ClinGen, G2P
• intellectual disability, X-linked 19

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• symptomatic form of Coffin-Lowry syndrome in female carriers

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=2.96 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004586.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA3	NM_004586.3	MANE Select	c.1308C>T	p.Cys436Cys	synonymous	Exon 15 of 22	NP_004577.1
	RPS6KA3	NM_001438340.1		c.1224C>T	p.Cys408Cys	synonymous	Exon 15 of 22	NP_001425269.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KA3	ENST00000379565.9	TSL:1 MANE Select	c.1308C>T	p.Cys436Cys	synonymous	Exon 15 of 22	ENSP00000368884.3
	RPS6KA3	ENST00000952699.1		c.1356C>T	p.Cys452Cys	synonymous	Exon 16 of 23	ENSP00000622758.1
	RPS6KA3	ENST00000916293.1		c.1326C>T	p.Cys442Cys	synonymous	Exon 15 of 22	ENSP00000586352.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000566 AC: 1 AN: 176760 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000227

GnomAD4 exome AF: 9.20e-7 AC: 1 AN: 1087470 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 353602

African (AFR) AF: 0.00 AC: 0 AN: 26196

American (AMR) AF: 0.0000286 AC: 1 AN: 35012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19266

East Asian (EAS) AF: 0.00 AC: 0 AN: 30047

South Asian (SAS) AF: 0.00 AC: 0 AN: 53661

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40391

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4095

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 833111

Other (OTH) AF: 0.00 AC: 0 AN: 45691

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.9
DANN	Benign	0.68
PhyloP100		3.0
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs1160828151; hg19: chrX-20190909;