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

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 18, 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:
RCV001238156.16

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]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001410955Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jul 18, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Phenotype and genotype in 103 patients with tricho-rhino-phalangeal syndrome.

Maas SM, Shaw AC, Bikker H, Lüdecke HJ, van der Tuin K, Badura-Stronka M, Belligni E, Biamino E, Bonati MT, Carvalho DR, Cobben J, de Man SA, Den Hollander NS, Di Donato N, Garavelli L, Grønborg S, Herkert JC, Hoogeboom AJ, Jamsheer A, Latos-Bielenska A, Maat-Kievit A, Magnani C, et al.

Eur J Med Genet. 2015 May;58(5):279-92. doi: 10.1016/j.ejmg.2015.03.002. Epub 2015 Mar 16.

PubMed [citation]
PMID:
25792522

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, SCV001410955.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This missense change has been observed in individuals with clinical features of tricho-rhino-phalangeal syndrome (PMID: 25792522; Invitae). It has also been observed to segregate with disease in related individuals. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Asn911 amino acid residue in TRPS1. Other variant(s) that disrupt this residue have been observed in individuals with TRPS1-related conditions (PMID: 25792522), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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"). ClinVar contains an entry for this variant (Variation ID: 438461). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 911 of the TRPS1 protein (p.Asn911Ser).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 10, 2024