rs793396

Variant names:

• chr3-4452187-G-A
• rs793396
• NM_182760.4:c.444+689C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-4452187-G-A
• chr3-4452187-G-T

Variant summary

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

The NM_182760.4(SUMF1):​c.444+689C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 150,536 control chromosomes in the GnomAD database, including 4,264 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 0.22 (4264 hom., cov: 31)
• Consequence: SUMF1 NM_182760.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948
• Publications: 6 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, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF1	NM_182760.4	MANE Select	c.444+689C>T		intron	N/A	NP_877437.2
	SUMF1	NM_001164675.2		c.444+689C>T		intron	N/A	NP_001158147.1	Q8NBK3-5
	SUMF1	NM_001164674.2		c.444+689C>T		intron	N/A	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.444+689C>T		intron	N/A	ENSP00000272902.5	Q8NBK3-1
	SUMF1	ENST00000405420.2	TSL:1	c.444+689C>T		intron	N/A	ENSP00000384977.2	Q8NBK3-5
	SUMF1	ENST00000948922.1		c.444+689C>T		intron	N/A	ENSP00000618981.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33256 AN: 150488 Hom.: 4267 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.00407

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.221 AC: 33255 AN: 150536 Hom.: 4264 Cov.: 31 AF XY: 0.216 AC XY: 15887 AN XY: 73438

African (AFR) AF: 0.119 AC: 4876 AN: 41020

American (AMR) AF: 0.212 AC: 3212 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 696 AN: 3468

East Asian (EAS) AF: 0.00427 AC: 22 AN: 5152

South Asian (SAS) AF: 0.113 AC: 539 AN: 4762

European-Finnish (FIN) AF: 0.300 AC: 2988 AN: 9952

Middle Eastern (MID) AF: 0.149 AC: 43 AN: 288

European-Non Finnish (NFE) AF: 0.299 AC: 20248 AN: 67774

Other (OTH) AF: 0.205 AC: 427 AN: 2078

Alfa AF: 0.247 Hom.: 2453

Bravo AF: 0.213

Asia WGS AF: 0.0620 AC: 215 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.67
PhyloP100		-0.95
Mutation Taster		=100/0	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: rs793396; hg19: chr3-4493871;