NM_002448.3(MSX1):c.487dup (p.Ala163fs) AND Hypoplastic enamel-onycholysis-hypohidrosis syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 26, 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:: RCV002829092.2

Allele description [Variation Report for NM_002448.3(MSX1):c.487dup (p.Ala163fs)]

NM_002448.3(MSX1):c.487dup (p.Ala163fs)

Gene:

MSX1:msh homeobox 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

4p16.2

Genomic location:

Preferred name:

NM_002448.3(MSX1):c.487dup (p.Ala163fs)

HGVS:

NC_000004.12:g.4862718dup
NG_008121.1:g.8054dup
NG_101971.1:g.509dup
NM_002448.3:c.487dupMANE SELECT
NP_002439.2:p.Ala163fs
LRG_1342t1:c.487dup
LRG_1342:g.8054dup
LRG_1342p1:p.Ala163fs
NC_000004.11:g.4864444_4864445insG
NC_000004.11:g.4864445dup

Protein change:

A163fs

Molecular consequence:

NM_002448.3:c.487dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hypoplastic enamel-onycholysis-hypohidrosis syndrome (TNS)
Synonyms:: NAIL DYSPLASIA WITH HYPODONTIA; Witkop syndrome; Dysplasia of nails with hypodontia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008582; MedGen: C0406735; Orphanet: 2228; OMIM: 189500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003212966	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 26, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30192788, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003212966

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 26, 2022)

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

Next generation sequencing reveals a novel nonsense mutation in MSX1 gene related to oligodontia.

Bonczek O, Bielik P, Krejčí P, Zeman T, Izakovičová-Hollá L, Šoukalová J, Vaněk J, Gerguri T, Balcar VJ, Šerý O.

PLoS One. 2018;13(9):e0202989. doi: 10.1371/journal.pone.0202989.

PubMed [citation]

PMID:: 30192788
PMCID:: PMC6128526

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, SCV003212966.2

#	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 disrupts a region of the MSX1 protein in which other variant(s) (p.Glu204*) have been determined to be pathogenic (PMID: 30192788; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This premature translational stop signal has been observed in individual(s) with oligodontia (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala163Glyfs*12) in the MSX1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 141 amino acid(s) of the MSX1 protein.

#	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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