NM_015295.3(SMCHD1):c.404G>A (p.Ser135Asn) 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:: RCV000417284.2

Allele description [Variation Report for NM_015295.3(SMCHD1):c.404G>A (p.Ser135Asn)]

NM_015295.3(SMCHD1):c.404G>A (p.Ser135Asn)

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.404G>A (p.Ser135Asn)

HGVS:

NC_000018.10:g.2667011G>A
NG_031972.1:g.16125G>A
NM_015295.3:c.404G>AMANE SELECT
NP_056110.2:p.Ser135Asn
NP_056110.2:p.Ser135Asn
NC_000018.9:g.2667010G>A
NM_015295.2:c.404G>A

Protein change:

S135N; SER135ASN

Links:

OMIM: 614982.0014; dbSNP: rs1057519646

NCBI 1000 Genomes Browser:

rs1057519646

Molecular consequence:

NM_015295.3:c.404G>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000328597	MGH Harvard Center for Reproductive Medicine, Massachusetts General Hospital	no assertion criteria provided	Pathogenic	de novo, unknown	research	PubMed (1) [See all records that cite this PMID]
SCV000503083	OMIM	no assertion criteria provided	Pathogenic (Feb 27, 2017)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 672092, 28067909, 28067911

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000328597

MGH Harvard Center for Reproductive Medicine, Massachusetts General Hospital

no assertion criteria provided

Pathogenic

de novo, unknown

research

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

SCV000503083

OMIM

no assertion criteria provided

Pathogenic
(Feb 27, 2017)

germline

literature only

PubMed (3)
[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	1	not provided	not provided	1	not provided	research
not provided	de novo	yes	1	not provided	not provided	1	not provided	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

[Familiary arhinia combined with peters' anomaly and maxilliar deformities, a new malformation syndrome (author's transl)].

Ruprecht KW, Majewski F.

Klin Monbl Augenheilkd. 1978 May;172(5):708-15. German.

PubMed [citation]

PMID:: 672092

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.

PubMed [citation]

PMID:: 28067909
PMCID:: PMC5473428

See all PubMed Citations (3)

Details of each submission

From MGH Harvard Center for Reproductive Medicine, Massachusetts General Hospital, SCV000328597.1

#	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)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	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

From OMIM, SCV000503083.1

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

Description

In a German woman (patient R1) with Bosma arhinia microphthalmia syndrome (BAMS; 603457), who was 1 of 2 affected sisters originally reported by Ruprecht and Majewski (1978), and in an unrelated affected Caucasian man (patient I1), Shaw et al. (2017) identified heterozygosity for a c.404G-A transition (c.404G-A, ENST00000320876.10) in exon 3 of the SMCHD1 gene, resulting in a ser135-to-asn (S135N) substitution at a highly conserved residue within the GHKL-type ATPase domain. The mutation was shown to have arisen de novo in the male proband, as it was not found in his unaffected parents; it was also not found in his 2 unaffected sisters.

Gordon et al. (2017) independently identified the S135N mutation in a 4-year-old North African boy with BAMS, in whom it arose de novo; they stated that the variant was not found in the ExAC, Exome Variant Server, or dbSNP (build 144) databases.

#	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: Mar 16, 2024

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