SUMF1 p.Ser359Ser

Variant names:

• chr3-4362191-T-T
• NM_182760.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr3-4362192--
• chr3-4362192-C-A
• chr3-4362192-C-G
• chr3-4362192-C-T
• chr3-4362192-CGA-ACT
• chr3-4362192-CGA-GCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_182760.4(SUMF1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SUMF1 NM_182760.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.90
• Publications: 0 publications found

Genes affected

SUMF1 (HGNC:20376): (sulfatase modifying factor 1) This gene encodes an enzyme that catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also known as C-alpha-formylglycine. Mutations in this gene cause multiple sulfatase deficiency, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

SUMF1 Gene-Disease associations (from GenCC):

• mucosulfatidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, PanelApp Australia, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182760.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF1	NM_182760.4	MANE Select	c.		exon_region	Exon 9 of 9	NP_877437.2
	SUMF1	NM_001164675.2		c.		exon_region	Exon 8 of 8	NP_001158147.1	Q8NBK3-5
	SUMF1	NM_001164674.2		c.		exon_region	Exon 8 of 8	NP_001158146.1	Q8NBK3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF1	ENST00000272902.10	TSL:1 MANE Select	c.		exon_region	Exon 9 of 9	ENSP00000272902.5	Q8NBK3-1
	SUMF1	ENST00000405420.2	TSL:1	c.		exon_region	Exon 8 of 8	ENSP00000384977.2	Q8NBK3-5
	SUMF1	ENST00000948922.1		c.		exon_region	Exon 9 of 9	ENSP00000618981.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-4403875;