ClinVar Genomic variation as it relates to human health
NM_182760.4(SUMF1):c.1045C>T (p.Arg349Trp)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_182760.4(SUMF1):c.1045C>T (p.Arg349Trp)
Variation ID: 2666 Accession: VCV000002666.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p26.1 3: 4362224 (GRCh38) [ NCBI UCSC ] 3: 4403908 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Aug 19, 2015 Feb 14, 2024 Feb 14, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_182760.4:c.1045C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_877437.2:p.Arg349Trp missense NM_001164674.2:c.970C>T NP_001158146.1:p.Arg324Trp missense NM_001164675.2:c.985C>T NP_001158147.1:p.Arg329Trp missense NC_000003.12:g.4362224G>A NC_000003.11:g.4403908G>A NG_016225.2:g.110059C>T Q8NBK3:p.Arg349Trp - Protein change
- R349W, R329W, R324W
- Other names
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- Canonical SPDI
- NC_000003.12:4362223:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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SUMF1 | - | - |
GRCh38 GRCh37 |
649 | 905 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (7) |
criteria provided, multiple submitters, no conflicts
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Feb 14, 2023 | RCV000002785.17 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 15, 2021 | RCV001582462.3 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Apr 27, 2019)
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criteria provided, single submitter
Method: clinical testing
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Multiple sulfatase deficiency
Affected status: no
Allele origin:
unknown
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Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV000930172.1
First in ClinVar: Aug 04, 2019 Last updated: Aug 04, 2019 |
Geographic origin: Iran
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Pathogenic
(Jun 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001819151.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
Published functional studies demonstrate a damaging effect (Cosma et al., 2004; Schlotawa et al., 2008); Not observed at a significant frequency in large population cohorts … (more)
Published functional studies demonstrate a damaging effect (Cosma et al., 2004; Schlotawa et al., 2008); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27535533, 32621519, 25885655, 15146462, 12757705, 18157819, 12757706, 17657823, 28452122, 20490930, 32620537, 19697114, 17881260, 24484558, 21224894, 29048999, 25373814, 30896912) (less)
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Pathogenic
(Sep 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Multiple sulfatase deficiency
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002027610.1
First in ClinVar: Nov 29, 2021 Last updated: Nov 29, 2021 |
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Pathogenic
(Dec 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Multiple sulfatase deficiency
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002791184.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Feb 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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Multiple sulfatase deficiency
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001382363.4
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
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 … (more)
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. (less)
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Pathogenic
(May 16, 2003)
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no assertion criteria provided
Method: literature only
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MULTIPLE SULFATASE DEFICIENCY
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000022943.2
First in ClinVar: Apr 04, 2013 Last updated: Aug 19, 2015 |
Comment on evidence:
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 … (more)
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). (less)
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Pathogenic
(Sep 01, 2021)
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no assertion criteria provided
Method: clinical testing
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Multiple sulfatase deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002079160.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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not provided
(-)
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no classification provided
Method: literature only
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Multiple sulfatase deficiency
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV000899285.2
First in ClinVar: May 02, 2019 Last updated: Oct 01, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Multiple Sulfatase Deficiency. | Adam MP | - | 2019 | PMID: 30896912 |
Natural disease history and characterisation of SUMF1 molecular defects in ten unrelated patients with multiple sulfatase deficiency. | Sabourdy F | Orphanet journal of rare diseases | 2015 | PMID: 25885655 |
Case of multiple sulfatase deficiency and ocular albinism: a diagnostic odyssey. | Prasad C | The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques | 2014 | PMID: 25373814 |
[Clinical characterization and mutation identification for multiple sulfatase deficiency patients in China]. | Meng Y | Zhonghua er ke za zhi = Chinese journal of pediatrics | 2013 | PMID: 24484558 |
Molecular analysis of SUMF1 mutations: stability and residual activity of mutant formylglycine-generating enzyme determine disease severity in multiple sulfatase deficiency. | Schlotawa L | Human mutation | 2008 | PMID: 18157819 |
Serial magnetic resonance imaging and neurophysiological studies in multiple sulphatase deficiency. | Zafeiriou DI | European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society | 2008 | PMID: 17881260 |
Multiple sulfatase deficiency is due to hypomorphic mutations of the SUMF1 gene. | Annunziata I | Human mutation | 2007 | PMID: 17657823 |
Molecular and functional analysis of SUMF1 mutations in multiple sulfatase deficiency. | Cosma MP | Human mutation | 2004 | PMID: 15146462 |
The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases. | Cosma MP | Cell | 2003 | PMID: 12757706 |
Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C(alpha)-formylglycine generating enzyme. | Dierks T | Cell | 2003 | PMID: 12757705 |
Text-mined citations for rs137852846 ...
HelpRecord last updated Feb 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.