NM_015295.3(SMCHD1):c.423G>C (p.Leu141Phe) AND Arrhinia with choanal atresia and microphthalmia syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 27, 2017
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000417278.2

Allele description [Variation Report for NM_015295.3(SMCHD1):c.423G>C (p.Leu141Phe)]

NM_015295.3(SMCHD1):c.423G>C (p.Leu141Phe)

Gene:

SMCHD1:structural maintenance of chromosomes flexible hinge domain containing 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18p11.32

Genomic location:

Preferred name:

NM_015295.3(SMCHD1):c.423G>C (p.Leu141Phe)

HGVS:

NC_000018.10:g.2667030G>C
NG_031972.1:g.16144G>C
NM_015295.3:c.423G>CMANE SELECT
NP_056110.2:p.Leu141Phe
NP_056110.2:p.Leu141Phe
NC_000018.9:g.2667029G>C
NM_015295.2:c.423G>C

Protein change:

L141F; LEU141PHE

Links:

OMIM: 614982.0009; dbSNP: rs1057519641

NCBI 1000 Genomes Browser:

rs1057519641

Molecular consequence:

NM_015295.3:c.423G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Arrhinia with choanal atresia and microphthalmia syndrome
Synonyms:: Arhinia choanal atresia microphthalmia; Bosma Henkin Christiansen syndrome; Congenital absence of nose and anterior nasopharynx; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011323; MedGen: C1863878; Orphanet: 1135; Orphanet: 2250; OMIM: 603457

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000328603	MGH Harvard Center for Reproductive Medicine, Massachusetts General Hospital	no assertion criteria provided	Pathogenic	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV000503077	OMIM	no assertion criteria provided	Pathogenic (Feb 27, 2017)	germline	literature only	PubMed (4) [See all records that cite these PMIDs] 5032329, 6802865, 23432817, 28067909

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000328603

MGH Harvard Center for Reproductive Medicine, Massachusetts General Hospital

no assertion criteria provided

Pathogenic

unknown

research

PubMed (1)
[See all records that cite this PMID]

SCV000503077

OMIM

no assertion criteria provided

Pathogenic
(Feb 27, 2017)

germline

literature only

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
not provided	unknown	yes	3	not provided	not provided	3	not provided	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Congenital absence of the nose and anterior nasopharynx. Report of two cases.

Gifford GH Jr, Swanson L, MacCollum DW.

Plast Reconstr Surg. 1972 Jul;50(1):5-12. No abstract available.

PubMed [citation]

PMID:: 5032329

Hypoplasia of the nose and eyes, hyposmia, hypogeusia, and hypogonadotrophic hypogonadism in two males.

Bosma JF, Henkin RI, Christiansen RL, Herdt JR.

J Craniofac Genet Dev Biol. 1981;1(2):153-84.

PubMed [citation]

PMID:: 6802865

See all PubMed Citations (4)

Details of each submission

From MGH Harvard Center for Reproductive Medicine, Massachusetts General Hospital, SCV000328603.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (1)
2	not provided	1	not provided	not provided	research	PubMed (1)
3	not provided	1	not provided	not provided	research	PubMed (1)

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

From OMIM, SCV000503077.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (4)

Description

In 4 unrelated probands with Bosma arhinia microphthalmia syndrome (BAMS; 603457), including a patient (patient E1) originally reported by Gifford et al. (1972) and also studied by Bosma et al. (1981), and another patient (patient C1) previously described by Tryggestad et al. (2013), Shaw et al. (2017) identified heterozygosity for a c.423G-C transversion (c.423G-C, ENST00000320876.10) in exon 3 of the SMCHD1 gene, resulting in a leu141-to-phe (L141F) substitution at a highly conserved residue within the GHKL-type ATPase domain. The mutation segregated with disease in the 2 families for which DNA was available from other family members, and was shown to have arisen de novo in a Swiss boy (patient V1). The authors noted that 1 of the patients (C1) did not exhibit the complete 'Bosma triad,' since he had arhinia and hypogonadism, but not microphthalmia.

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

Last Updated: Apr 23, 2022

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