NM_004273.5(CHST3):c.1150_1166del (p.Glu384fs) AND Spondyloepiphyseal dysplasia with congenital joint dislocations

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 14, 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:: RCV001999870.4

Allele description [Variation Report for NM_004273.5(CHST3):c.1150_1166del (p.Glu384fs)]

NM_004273.5(CHST3):c.1150_1166del (p.Glu384fs)

Gene:

CHST3:carbohydrate sulfotransferase 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

10q22.1

Genomic location:

Preferred name:

NM_004273.5(CHST3):c.1150_1166del (p.Glu384fs)

HGVS:

NC_000010.11:g.72008181_72008197del
NG_012635.1:g.48820_48836del
NM_004273.5:c.1150_1166delMANE SELECT
NP_004264.2:p.Glu384fs
NC_000010.10:g.73767936_73767952del
NC_000010.10:g.73767939_73767955del

Protein change:

E384fs

Links:

dbSNP: rs2131776376

NCBI 1000 Genomes Browser:

rs2131776376

Molecular consequence:

NM_004273.5:c.1150_1166del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Spondyloepiphyseal dysplasia with congenital joint dislocations (SEDCJD)
Synonyms:: Kozlowski Celermajer Tink syndrome; Humero-spinal dysostosis with congenital heart disease
Identifiers:: MONDO: MONDO:0007738; MedGen: C1837657; Orphanet: 263463; OMIM: 143095

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F-box protein PP2-A15 isoform X2 [Cucurbita pepo subsp. pepo]
F-box protein PP2-A15 isoform X2 [Cucurbita pepo subsp. pepo]
gi|1333132042|ref|XP_023540673.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002233596	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 14, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29453417, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002233596

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 14, 2021)

germline

clinical testing

PubMed (2)
[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

Exome sequencing has higher diagnostic yield compared to simulated disease-specific panels in children with suspected monogenic disorders.

Dillon OJ, Lunke S, Stark Z, Yeung A, Thorne N; Melbourne Genomics Health Alliance., Gaff C, White SM, Tan TY.

Eur J Hum Genet. 2018 May;26(5):644-651. doi: 10.1038/s41431-018-0099-1. Epub 2018 Feb 16.

PubMed [citation]

PMID:: 29453417
PMCID:: PMC5945679

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002233596.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant results in an extension of the CHST3 protein. Other variant(s) that result in a similarly extended protein product (p.Ser431Lysfs*81) have been determined to be pathogenic (PMID: 29453417; Invitae). This suggests that these extensions are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with CHST3-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change results in a frameshift in the CHST3 gene (p.Glu384Argfs*122). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 96 amino acid(s) of the CHST3 protein and extend the protein by 25 additional amino acid residues.

#	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: Sep 29, 2024

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