NM_182760.4(SUMF1):c.1045C>T (p.Arg349Trp) AND Multiple sulfatase deficiency

Germline classification:: Pathogenic/Likely pathogenic (7 submissions)
Last evaluated:: Feb 14, 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:: RCV000002785.17

Allele description [Variation Report for NM_182760.4(SUMF1):c.1045C>T (p.Arg349Trp)]

NM_182760.4(SUMF1):c.1045C>T (p.Arg349Trp)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

3p26.1

Genomic location:

Preferred name:

NM_182760.4(SUMF1):c.1045C>T (p.Arg349Trp)

HGVS:

NC_000003.12:g.4362224G>A
NG_016225.2:g.110059C>T
NM_001164674.2:c.970C>T
NM_001164675.2:c.985C>T
NM_182760.4:c.1045C>TMANE SELECT
NP_001158146.1:p.Arg324Trp
NP_001158147.1:p.Arg329Trp
NP_877437.2:p.Arg349Trp
NC_000003.11:g.4403908G>A
NM_182760.3:c.1045C>T
Q8NBK3:p.Arg349Trp

Protein change:

R324W; ARG349TRP

Links:

UniProtKB: Q8NBK3#VAR_016060; OMIM: 607939.0004; dbSNP: rs137852846

NCBI 1000 Genomes Browser:

rs137852846

Molecular consequence:

NM_001164674.2:c.970C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001164675.2:c.985C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_182760.4:c.1045C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000022943	OMIM	no assertion criteria provided	Pathogenic (May 16, 2003)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 12757705, 12757706
SCV000899285	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000930172	Genomic Research Center, Shahid Beheshti University of Medical Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 27, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001382363	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 14, 2023)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 12757705, 12757706, 17881260, 24484558, 25373814, 25885655, 15146462, 17657823, 18157819, 28492532
SCV002027610	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]
SCV002079160	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 1, 2021)	germline	clinical testing
SCV002791184	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 15, 2021)	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	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, literature only
not provided	unknown	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Multiple Sulfatase Deficiency.

Schlotawa L, Adang L, De Castro M, Ahrens-Nicklas R.

2019 Mar 21. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]

PMID:: 30896912

Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C(alpha)-formylglycine generating enzyme.

Dierks T, Schmidt B, Borissenko LV, Peng J, Preusser A, Mariappan M, von Figura K.

Cell. 2003 May 16;113(4):435-44.

PubMed [citation]

PMID:: 12757705

See all PubMed Citations (12)

Details of each submission

From OMIM, SCV000022943.2

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

Description

In patients with multiple sulfatase deficiency (MSD; 272200), Dierks et al. (2003) and Cosma et al. (2003) identified homozygosity for a C-to-T transition at nucleotide 1045 of the SUMF1 gene, resulting in the substitution of a conserved amino acid, arg349 to trp (R349W).

#	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 GeneReviews, SCV000899285.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	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 Genomic Research Center, Shahid Beheshti University of Medical Sciences, SCV000930172.1

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

From Invitae, SCV001382363.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 349 of the SUMF1 protein (p.Arg349Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with multiple sulfatase deficiency (PMID: 12757705, 12757706, 15146462, 17881260, 18157819, 24484558, 25373814, 25885655). ClinVar contains an entry for this variant (Variation ID: 2666). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SUMF1 protein function. Experimental studies have shown that this missense change affects SUMF1 function (PMID: 15146462, 17657823, 18157819). 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 Genome-Nilou Lab, SCV002027610.1

#	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

From Natera, Inc., SCV002079160.1

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

#	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 Fulgent Genetics, Fulgent Genetics, SCV002791184.1

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

Last Updated: Feb 20, 2024

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