NM_020928.2(ZSWIM6):c.3487C>T (p.Arg1163Trp) AND Acromelic frontonasal dysostosis

Germline classification:: Pathogenic/Likely pathogenic (6 submissions)
Last evaluated:: Nov 10, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000143865.11

Allele description [Variation Report for NM_020928.2(ZSWIM6):c.3487C>T (p.Arg1163Trp)]

NM_020928.2(ZSWIM6):c.3487C>T (p.Arg1163Trp)

Gene:

ZSWIM6:zinc finger SWIM-type containing 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q12.1

Genomic location:

Preferred name:

NM_020928.2(ZSWIM6):c.3487C>T (p.Arg1163Trp)

HGVS:

NC_000005.10:g.61544156C>T
NG_053150.1:g.216884C>T
NM_020928.2:c.3487C>TMANE SELECT
NP_065979.1:p.Arg1163Trp
NC_000005.9:g.60839983C>T
NM_020928.1:c.3487C>T
Q9HCJ5:p.Arg1163Trp

Protein change:

R1163W; ARG1163TRP

Links:

UniProtKB: Q9HCJ5#VAR_071802; OMIM: 615951.0001; dbSNP: rs587777695

NCBI 1000 Genomes Browser:

rs587777695

Molecular consequence:

NM_020928.2:c.3487C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Acromelic frontonasal dysostosis (AFND)
Identifiers:: MONDO: MONDO:0011359; MedGen: C1863616; Orphanet: 1827; OMIM: 603671

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
SCV000188733	OMIM	no assertion criteria provided	Pathogenic (Aug 7, 2014)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 25105228, 26706854
SCV000246129	University of Washington Center for Mendelian Genomics, University of Washington	criteria provided, single submitter (submitter's publication)	Pathogenic (Sep 23, 2014)	de novo	research	PubMed (1) [See all records that cite this PMID]
SCV000803459	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 31, 2018)	unknown	curation	PubMed (3) [See all records that cite these PMIDs] 25105228, 26706854, 25741868
SCV000803852	Equipe Genetique des Anomalies du Developpement, Université de Bourgogne - Clinvar_gadteam_Clinical_exome_analysis_3	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 11, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000986913	GenomeConnect, ClinGen	no classification provided	not provided	unknown	phenotyping only
SCV004102654	Daryl Scott Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 10, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation, phenotyping only
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Exome sequencing identifies a recurrent de novo ZSWIM6 mutation associated with acromelic frontonasal dysostosis.

Smith JD, Hing AV, Clarke CM, Johnson NM, Perez FA, Park SS, Horst JA, Mecham B, Maves L, Nickerson DA; University of Washington Center for Mendelian Genomics, Cunningham ML.

Am J Hum Genet. 2014 Aug 7;95(2):235-40. doi: 10.1016/j.ajhg.2014.07.008.

PubMed [citation]

PMID:: 25105228
PMCID:: PMC4129399

Acromelic frontonasal dysostosis and ZSWIM6 mutation: phenotypic spectrum and mosaicism.

Twigg SR, Ousager LB, Miller KA, Zhou Y, Elalaoui SC, Sefiani A, Bak GS, Hove H, Hansen LK, Fagerberg CR, Tajir M, Wilkie AO.

Clin Genet. 2016 Sep;90(3):270-5. doi: 10.1111/cge.12721. Epub 2016 Feb 3.

PubMed [citation]

PMID:: 26706854
PMCID:: PMC5025718

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000188733.3

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

Description

In 4 unrelated patients with acromelic frontonasal dysostosis (AFND; 603671), Smith et al. (2014) identified heterozygosity for a de novo c.3487C-T transition in exon 14 of the ZSWIM6 gene, resulting in an arg1163-to-trp (R1163W) substitution at a highly conserved residue in the SIN3-like domain. In the most mildly affected patient, the mutation was present at a 60:40 ratio of wildtype to mutant allele, suggestive of mosaicism.

In 2 sporadic patients with AFND and the severely affected son of a mildly affected woman, Twigg et al. (2016) identified heterozygosity for the R1163W mutation in the ZSWIM6 gene. Deep sequencing of DNA in 5 tissues from the mildly affected mother confirmed mosaicism for the mutation, with the variant allele being present at approximately 11% in buccal scrapings, 3% in saliva, 2% in urine and blood, and 1% in skin.

#	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

From University of Washington Center for Mendelian Genomics, University of Washington, SCV000246129.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	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	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From SIB Swiss Institute of Bioinformatics, SCV000803459.1

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

Description

This variant is interpreted as a Likely Pathogenic, for Acromelic frontonasal dysostosis, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: PM6 => Assumed de novo, but without confirmation of paternity and maternity (PMID:25105228). PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => Observed in multiple unrelated patients. (PMID:25105228,26706854).

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

From Equipe Genetique des Anomalies du Developpement, Université de Bourgogne - Clinvar_gadteam_Clinical_exome_analysis_3, SCV000803852.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

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

From GenomeConnect, ClinGen, SCV000986913.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	phenotyping only	not provided

Description

Variant interpretted as pathogenic and reported on 09/20/2018 by GTR ID 239772. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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

From Daryl Scott Lab, Baylor College of Medicine, SCV004102654.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

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

Last Updated: Oct 20, 2024

ClinVar

Relating variation to medicine