NM_004586.3(RPS6KA3):c.727C>T (p.Arg243Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 8, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000807329.4

Allele description [Variation Report for NM_004586.3(RPS6KA3):c.727C>T (p.Arg243Ter)]

NM_004586.3(RPS6KA3):c.727C>T (p.Arg243Ter)

Gene:

RPS6KA3:ribosomal protein S6 kinase A3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp22.12

Genomic location:

Preferred name:

NM_004586.3(RPS6KA3):c.727C>T (p.Arg243Ter)

HGVS:

NC_000023.11:g.20187875G>A
NG_007488.1:g.83758C>T
NM_004586.3:c.727C>TMANE SELECT
NP_004577.1:p.Arg243Ter
NC_000023.10:g.20205993G>A
NM_004586.2:c.727C>T

Protein change:

R243*

Links:

dbSNP: rs1603425345

NCBI 1000 Genomes Browser:

rs1603425345

Molecular consequence:

NM_004586.3:c.727C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Coffin-Lowry syndrome (CLS)
Synonyms:: Mental retardation with osteocartilaginous abnormalities; Coffin syndrome; COFFIN-LOWRY SYNDROME, MILD
Identifiers:: MONDO: MONDO:0010561; MedGen: C0265252; Orphanet: 192; OMIM: 303600

Name:: Intellectual disability, X-linked 19 (XLID19)
Synonyms:: INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 19
Identifiers:: MONDO: MONDO:0010447; MedGen: C0796225; Orphanet: 777; OMIM: 300844

Recent activity

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homogentisate 1,2-dioxygenase [Mus musculus]
homogentisate 1,2-dioxygenase [Mus musculus]
gi|240120123|ref|NP_038575.2|

Protein
Chain K, Leucine-rich repeat and death domain-containing protein
Chain K, Leucine-rich repeat and death domain-containing protein
gi|146387317|pdb|2OF5|K

Protein
Chain C, RECA
Chain C, RECA
gi|2098392|pdb|2REC|C

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000947376	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 8, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11180593, 9837815, 19888300, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000947376

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 8, 2021)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the X-linked RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome.

Delaunoy J, Abidi F, Zeniou M, Jacquot S, Merienne K, Pannetier S, Schmitt M, Schwartz C, Hanauer A.

Hum Mutat. 2001 Feb;17(2):103-16.

PubMed [citation]

PMID:: 11180593

Mutation analysis of the RSK2 gene in Coffin-Lowry patients: extensive allelic heterogeneity and a high rate of de novo mutations.

Jacquot S, Merienne K, De Cesare D, Pannetier S, Mandel JL, Sassone-Corsi P, Hanauer A.

Am J Hum Genet. 1998 Dec;63(6):1631-40.

PubMed [citation]

PMID:: 9837815
PMCID:: PMC1377634

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000947376.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individuals with Coffin-Lowry syndrome (PMID: 11180593). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg243*) in the RPS6KA3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RPS6KA3 are known to be pathogenic (PMID: 9837815, 19888300).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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