NM_000977.4(RPL13):c.477+1G>A AND Spondyloepimetaphyseal dysplasia, Isidor-Toutain type

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 27, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000991038.5

Allele description [Variation Report for NM_000977.4(RPL13):c.477+1G>A]

NM_000977.4(RPL13):c.477+1G>A

Gene:

RPL13:ribosomal protein L13 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_000977.4(RPL13):c.477+1G>A

HGVS:

NC_000016.10:g.89562392G>A
NM_000977.4:c.477+1G>AMANE SELECT
NM_001243131.1:c.336+1G>A
NM_033251.2:c.477+1G>A
NC_000016.9:g.89628800G>A
NC_000016.9:g.89628800G>A
NM_000977.3:c.477+1G>A

Nucleotide change:

IVS5DS, G-A, +1

Links:

OMIM: 113703.0003; dbSNP: rs1597675888

NCBI 1000 Genomes Browser:

rs1597675888

Molecular consequence:

NM_000977.4:c.477+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001243131.1:c.336+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_033251.2:c.477+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Functional consequence:

Variation affecting splicing function of RNA [Variation Ontology: 0397] - Comment(s)

Observations:

Condition(s)

Name:: Spondyloepimetaphyseal dysplasia, Isidor-Toutain type
Identifiers:: MONDO: MONDO:0032885; MedGen: C5231478; OMIM: 618728

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001142142	OMIM	no assertion criteria provided	Pathogenic (Jan 6, 2020)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001432138	Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 1, 2020)	paternal, unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31630789, 25741868
SCV003935993	Rare Disease Group, Clinical Genetics, Karolinska Institutet	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 27, 2023)	paternal	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001142142

OMIM

no assertion criteria provided

Pathogenic
(Jan 6, 2020)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV001432138

Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 1, 2020)

paternal, unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV003935993

Rare Disease Group, Clinical Genetics, Karolinska Institutet

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 27, 2023)

paternal

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	paternal	yes	2	not provided	not provided	2	yes	clinical testing
not provided	unknown	yes	1	not provided	not provided	1	yes	clinical testing

Citations

PubMed

RPL13 Variants Cause Spondyloepimetaphyseal Dysplasia with Severe Short Stature.

Le Caignec C, Ory B, Lamoureux F, O'Donohue MF, Orgebin E, Lindenbaum P, Téletchéa S, Saby M, Hurst A, Nelson K, Gilbert SR, Wilnai Y, Zeitlin L, Segev E, Tesfaye R, Nizon M, Cogne B, Bezieau S, Geoffroy L, Hamel A, Mayrargue E, de Courtivron B, et al.

Am J Hum Genet. 2019 Nov 7;105(5):1040-1047. doi: 10.1016/j.ajhg.2019.09.024. Epub 2019 Oct 17.

PubMed [citation]

PMID:: 31630789
PMCID:: PMC6849359

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV001142142.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a male patient (P3) with the Isidor-Toutain type of spondyloepimetaphyseal dysplasia (SEMDIST; 618728), Le Caignec et al. (2019) identified heterozygosity for a de novo splicing mutation (c.477+1G-A, NM_000977.3) in intron 5 of the RPL13 gene, leading to an 18-amino acid insertion (Asn159_Val160ins18). The mutation was not found in the ExAC/gnomAD databases.

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

From Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN, SCV001432138.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	yes	clinical testing	PubMed (2)
2	not provided	1	not provided	yes	clinical testing	PubMed (2)
3	not provided	1	not provided	yes	clinical testing	PubMed (2)

Description

This variant segregates in multiple affected individuals in the same family (proband, father, and paternal half-sister).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	paternal	yes	1	blood	not provided		1	not provided	not provided	not provided
2	paternal	yes	1	blood	not provided		1	not provided	not provided	not provided
3	unknown	yes	1	blood	not provided		1	not provided	not provided	not provided

From Rare Disease Group, Clinical Genetics, Karolinska Institutet, SCV003935993.1

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

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

Last Updated: May 7, 2024

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