NM_015295.3(SMCHD1):c.410G>A (p.Gly137Glu) AND Arrhinia with choanal atresia and microphthalmia syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 1, 2012
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:: RCV000417296.3

Allele description [Variation Report for NM_015295.3(SMCHD1):c.410G>A (p.Gly137Glu)]

NM_015295.3(SMCHD1):c.410G>A (p.Gly137Glu)

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.410G>A (p.Gly137Glu)

HGVS:

NC_000018.10:g.2667017G>A
NG_031972.1:g.16131G>A
NM_015295.3:c.410G>AMANE SELECT
NP_056110.2:p.Gly137Glu
NP_056110.2:p.Gly137Glu
NC_000018.9:g.2667016G>A
NM_015295.2:c.410G>A

Protein change:

G137E; GLY137GLU

Links:

OMIM: 614982.0012; dbSNP: rs1057519644

NCBI 1000 Genomes Browser:

rs1057519644

Molecular consequence:

NM_015295.3:c.410G>A - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000328601	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]
SCV000503080	OMIM	no assertion criteria provided	Pathogenic (Dec 1, 2012)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 28067909, 23143600

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000328601

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]

SCV000503080

OMIM

no assertion criteria provided

Pathogenic
(Dec 1, 2012)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	1	not provided	not provided	1	not provided	research

Citations

PubMed

SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome.

Shaw ND, Brand H, Kupchinsky ZA, Bengani H, Plummer L, Jones TI, Erdin S, Williamson KA, Rainger J, Stortchevoi A, Samocha K, Currall BB, Dunican DS, Collins RL, Willer JR, Lek A, Lek M, Nassan M, Pereira S, Kammin T, Lucente D, Silva A, et al.

Nat Genet. 2017 Feb;49(2):238-248. doi: 10.1038/ng.3743. Epub 2017 Jan 9. Erratum in: Nat Genet. 2017 May 26;49(6):969. doi: 10.1038/ng0617-969c.

PubMed [citation]

PMID:: 28067909
PMCID:: PMC5473428

Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2.

Lemmers RJ, Tawil R, Petek LM, Balog J, Block GJ, Santen GW, Amell AM, van der Vliet PJ, Almomani R, Straasheijm KR, Krom YD, Klooster R, Sun Y, den Dunnen JT, Helmer Q, Donlin-Smith CM, Padberg GW, van Engelen BG, de Greef JC, Aartsma-Rus AM, Frants RR, de Visser M, et al.

Nat Genet. 2012 Dec;44(12):1370-4. doi: 10.1038/ng.2454. Epub 2012 Nov 11.

PubMed [citation]

PMID:: 23143600
PMCID:: PMC3671095

Details of each submission

From MGH Harvard Center for Reproductive Medicine, Massachusetts General Hospital, SCV000328601.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	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

From OMIM, SCV000503080.2

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

Description

In a 17-year-old African American girl (patient AG1) with Bosma arhinia microphthalmia syndrome (BAMS; 603457), Shaw et al. (2017) identified heterozygosity for a c.410G-A transition (c.410G-A, ENST00000320876.10) in exon 3 of the SMCHD1 gene, resulting in a gly137-to-glu (G137E) substitution at a highly conserved residue within the GHKL-type ATPase domain. Shaw et al. (2017) noted that the G137E mutation had previously been reported in a patient with facioscapulohumeral muscular dystrophy-2 (FSHD2; 158901) by Lemmers et al. (2012).

#	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: May 7, 2024

ClinVar

Relating variation to medicine