NM_014112.5(TRPS1):c.3374G>A (p.Arg1125Gln) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 10, 2022
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:: RCV003806790.2

Allele description [Variation Report for NM_014112.5(TRPS1):c.3374G>A (p.Arg1125Gln)]

NM_014112.5(TRPS1):c.3374G>A (p.Arg1125Gln)

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.3374G>A (p.Arg1125Gln)

HGVS:

NC_000008.11:g.115414534C>T
NG_012383.3:g.259468G>A
NM_001282902.3:c.3347G>A
NM_001282903.3:c.3353G>A
NM_001330599.2:c.3335G>A
NM_014112.5:c.3374G>AMANE SELECT
NP_001269831.1:p.Arg1116Gln
NP_001269832.1:p.Arg1118Gln
NP_001317528.1:p.Arg1112Gln
NP_054831.2:p.Arg1125Gln
NC_000008.10:g.116426762C>T

Protein change:

R1112Q

Molecular consequence:

NM_001282902.3:c.3347G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282903.3:c.3353G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330599.2:c.3335G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_014112.5:c.3374G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Trichorhinophalangeal syndrome, type III (TRPS3)
Synonyms:: Trichorhinophalangeal syndrome type 3; TRPS 3; Sugio-Kajii Syndrome
Identifiers:: MONDO: MONDO:0008597; MedGen: C1860823; Orphanet: 77258; OMIM: 190351

Name:: Trichorhinophalangeal dysplasia type I (TRPS1)
Synonyms:: TRPS I; Trichorhinophalangeal syndrome type 1; Giedion syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008596; MedGen: C0432233; Orphanet: 77258; OMIM: 190350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004596909	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 10, 2022)	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

SCV004596909

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 10, 2022)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004596909.1

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

Description

This variant has not been reported in the literature in individuals affected with TRPS1-related conditions. This variant is present in population databases (rs773593651, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1125 of the TRPS1 protein (p.Arg1125Gln). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TRPS1 protein function. 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: Sep 29, 2024

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