NM_004273.5(CHST3):c.773C>G (p.Thr258Arg) AND Spondyloepiphyseal dysplasia with congenital joint dislocations

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 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:: RCV002020829.3

Allele description [Variation Report for NM_004273.5(CHST3):c.773C>G (p.Thr258Arg)]

NM_004273.5(CHST3):c.773C>G (p.Thr258Arg)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

10q22.1

Genomic location:

Preferred name:

NM_004273.5(CHST3):c.773C>G (p.Thr258Arg)

HGVS:

NC_000010.11:g.72007804C>G
NG_012635.1:g.48443C>G
NM_004273.5:c.773C>GMANE SELECT
NP_004264.2:p.Thr258Arg
NC_000010.10:g.73767562C>G

Protein change:

T258R

Links:

dbSNP: rs1840059581

NCBI 1000 Genomes Browser:

rs1840059581

Molecular consequence:

NM_004273.5:c.773C>G - missense variant - [Sequence Ontology: SO:0001583]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002304747	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 14, 2021)	germline	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

SCV002304747

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 14, 2021)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Invitae, SCV002304747.3

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

Description

This sequence change replaces threonine with arginine at codon 258 of the CHST3 protein (p.Thr258Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CHST3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 20, 2024

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