NM_182760.4(SUMF1):c.691dup (p.Trp231fs) AND Multiple sulfatase deficiency

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Dec 9, 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:: RCV001193352.11

Allele description [Variation Report for NM_182760.4(SUMF1):c.691dup (p.Trp231fs)]

NM_182760.4(SUMF1):c.691dup (p.Trp231fs)

Gene:

SUMF1:sulfatase modifying factor 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

3p26.1

Genomic location:

Preferred name:

NM_182760.4(SUMF1):c.691dup (p.Trp231fs)

HGVS:

NC_000003.12:g.4418044dup
NG_016225.2:g.54239dup
NM_001164674.2:c.616dup
NM_001164675.2:c.691dup
NM_182760.4:c.691dupMANE SELECT
NP_001158146.1:p.Trp206fs
NP_001158147.1:p.Trp231fs
NP_877437.2:p.Trp231fs
NC_000003.11:g.4459727_4459728insA
NC_000003.11:g.4459728dup
NM_182760.3:c.691dup
NM_182760.3:c.691dupT

Protein change:

W206fs

Links:

dbSNP: rs748337915

NCBI 1000 Genomes Browser:

rs748337915

Molecular consequence:

NM_001164674.2:c.616dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001164675.2:c.691dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_182760.4:c.691dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Multiple sulfatase deficiency (MSD)
Synonyms:: Juvenile sulfatidosis; Mucosulfatidosis; Multiple Sulfatase Deficiency Disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010088; MedGen: C0268263; Orphanet: 585; OMIM: 272200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001362110	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Feb 7, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27391121, 25222778, 33686258 Citation Link,
SCV001591306	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 9, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 12757705, 12757706, 25885655, 25222778, 28492532
SCV002021989	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 2, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002027611	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 5, 2021)	germline	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	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Whole exome sequencing diagnosis of inborn errors of metabolism and other disorders in United Arab Emirates.

Al-Shamsi A, Hertecant JL, Souid AK, Al-Jasmi FA.

Orphanet J Rare Dis. 2016 Jul 8;11(1):94. doi: 10.1186/s13023-016-0474-3.

PubMed [citation]

PMID:: 27391121
PMCID:: PMC4939014

High diagnosis rate for nonimmune hydrops fetalis with prenatal clinical exome from the Hydrops-Yielding Diagnostic Results of Prenatal Sequencing (HYDROPS) Study.

Al-Kouatly HB, Makhamreh MM, Rice SM, Smith K, Harman C, Quinn A, Valcarcel BN, Firman B, Liu R, Hegde M, Critchlow E, Berger SI.

Genet Med. 2021 Jul;23(7):1325-1333. doi: 10.1038/s41436-021-01121-0. Epub 2021 Mar 8.

PubMed [citation]

PMID:: 33686258

See all PubMed Citations (8)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362110.2

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

Description

Variant summary: SUMF1 c.691dupT (p.Trp231LeufsX11) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2.4e-05 in 251400 control chromosomes. c.691dupT has been reported in the literature in individuals affected with Multiple Sulfatase Deficiency (Kotecha_2014, Al-Shamsi_2016, Al-Kouatly_2021). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001591306.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Trp231Leufs*11) in the SUMF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SUMF1 are known to be pathogenic (PMID: 12757705, 12757706, 25885655). This variant is present in population databases (rs748337915, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with multiple sulphatase deficiency (PMID: 25222778). ClinVar contains an entry for this variant (Variation ID: 928845). For these reasons, this variant has been classified as Pathogenic.

#	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

From Revvity Omics, Revvity, SCV002021989.3

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002027611.1

#	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	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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