NM_014112.5(TRPS1):c.2732A>G (p.Asn911Ser) AND Metaphyseal chondrodysplasia

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 5, 2024
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:: RCV003883488.1

Allele description [Variation Report for NM_014112.5(TRPS1):c.2732A>G (p.Asn911Ser)]

NM_014112.5(TRPS1):c.2732A>G (p.Asn911Ser)

Gene:

TRPS1:transcriptional repressor GATA binding 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q23.3

Genomic location:

Preferred name:

NM_014112.5(TRPS1):c.2732A>G (p.Asn911Ser)

HGVS:

NC_000008.11:g.115418421T>C
NG_012383.3:g.255581A>G
NG_053427.1:g.55T>C
NM_001282902.3:c.2705A>G
NM_001282903.3:c.2711A>G
NM_001330599.2:c.2693A>G
NM_014112.5:c.2732A>GMANE SELECT
NP_001269831.1:p.Asn902Ser
NP_001269832.1:p.Asn904Ser
NP_001317528.1:p.Asn898Ser
NP_054831.2:p.Asn911Ser
NP_054831.2:p.Asn911Ser
NC_000008.10:g.116430649T>C
NM_014112.4:c.2732A>G

Protein change:

N898S

Links:

dbSNP: rs1554617580

NCBI 1000 Genomes Browser:

rs1554617580

Molecular consequence:

NM_001282902.3:c.2705A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282903.3:c.2711A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001330599.2:c.2693A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_014112.5:c.2732A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Metaphyseal chondrodysplasia
Synonyms:: Metaphyseal chondrodysplasia (disease)
Identifiers:: MONDO: MONDO:0000138; MedGen: C0265290; Human Phenotype Ontology: HP:0005871

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004698006	Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 5, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 31502745, 28426188, 25792522, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004698006

Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 5, 2024)

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
Caucasian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Multiplex targeted high-throughput sequencing in a series of 352 patients with congenital limb malformations.

Jourdain AS, Petit F, Odou MF, Balduyck M, Brunelle P, Dufour W, Boussion S, Brischoux-Boucher E, Colson C, Dieux A, Gérard M, Ghoumid J, Giuliano F, Goldenberg A, Khau Van Kien P, Lehalle D, Morin G, Moutton S, Smol T, Vanlerberghe C, Manouvrier-Hanu S, Escande F.

Hum Mutat. 2020 Jan;41(1):222-239. doi: 10.1002/humu.23912. Epub 2019 Sep 23.

PubMed [citation]

PMID:: 31502745

Trichorhinophalangeal Syndrome..

Tüysüz B, Güneş N, Alkaya DU.

2017 Apr 20 [updated 2024 Mar 21]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]

PMID:: 28426188

See all PubMed Citations (4)

Details of each submission

From Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations, SCV004698006.1

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

Description

We observed de novo variant NM_014112:c.2732A>G (p.Asn911Ser) in the TRPS1 gene in female proband (33 y.o., Caucasian) with metaphyseal chondrodysplasia with alopecia (parenthood was not tested). No additional rare candidate variants (Class III-V of pathogenicity) were found in this proband. This variant is absent in The Genome Aggregation Database (gnomAD) v2.1.1 and v4.0.0 (Date of access with 04-03-2024). Clinvar contains an entry for this variant (Variation ID: 438461). This variant has been reported in 3 publications in patients with variable phenotypes (PMID: 31502745, 28426188, 25792522). This variants is located in zinc finger domain GATA-type AA 896-920 and alternative change NM_014112:c.2731A>T (p.Asn911Tyr) have been classified as Likely Pathogenic (ACMG: PM1, PM2, PP3, PP5). Most in silico predictors show pathogenic result of the protein change (varsome.com). In accordance with ACMG(2015) this variant is classified as Likely Pathogenic with following criteria selected: PM1, PM2, PM5_supporting, PM6, PP3, PP5.

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

Last Updated: Nov 24, 2024

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