3-4395674-T-C

Variant names:

• chr3-4395674-T-C
• rs794185
• NM_182760.4:c.954+15191A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182760.4(SUMF1):​c.954+15191A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,074 control chromosomes in the GnomAD database, including 14,975 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (14975 hom., cov: 32)
• Consequence: SUMF1 NM_182760.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• Publications: 29 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: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF1	NM_182760.4	MANE Select	c.954+15191A>G		intron	N/A	NP_877437.2
	SUMF1	NM_001164675.2		c.954+15191A>G		intron	N/A	NP_001158147.1
	SUMF1	NM_001164674.2		c.879+15191A>G		intron	N/A	NP_001158146.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF1	ENST00000272902.10	TSL:1 MANE Select	c.954+15191A>G		intron	N/A	ENSP00000272902.5
	SUMF1	ENST00000405420.2	TSL:1	c.954+15191A>G		intron	N/A	ENSP00000384977.2
	SUMF1	ENST00000383843.9	TSL:2	c.879+15191A>G		intron	N/A	ENSP00000373355.5

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66799 AN: 151956 Hom.: 14964 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.399

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.440 AC: 66867 AN: 152074 Hom.: 14975 Cov.: 32 AF XY: 0.434 AC XY: 32280 AN XY: 74310

African (AFR) AF: 0.496 AC: 20576 AN: 41506

American (AMR) AF: 0.458 AC: 6996 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1269 AN: 3468

East Asian (EAS) AF: 0.314 AC: 1627 AN: 5174

South Asian (SAS) AF: 0.275 AC: 1326 AN: 4824

European-Finnish (FIN) AF: 0.411 AC: 4339 AN: 10554

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29322 AN: 67964

Other (OTH) AF: 0.397 AC: 840 AN: 2114

Alfa AF: 0.427 Hom.: 65636

Bravo AF: 0.451

Asia WGS AF: 0.297 AC: 1032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.29
PhyloP100		-0.96
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs794185; hg19: chr3-4437358; COSMIC: COSV55994075;