rs711635

Variant names:

• chr3-4448829-G-A
• rs711635
• NM_182760.4:c.519+437C>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.519+437C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,068 control chromosomes in the GnomAD database, including 10,218 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 0.36 (10218 hom., cov: 32)
• Consequence: SUMF1 NM_182760.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113
• Publications: 7 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 (NFE) allele frequency at 95% confidence interval = 0.385 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.519+437C>T		intron	N/A	NP_877437.2
	SUMF1	NM_001164675.2		c.519+437C>T		intron	N/A	NP_001158147.1
	SUMF1	NM_001164674.2		c.444+4047C>T		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.519+437C>T		intron	N/A	ENSP00000272902.5
	SUMF1	ENST00000405420.2	TSL:1	c.519+437C>T		intron	N/A	ENSP00000384977.2
	SUMF1	ENST00000383843.9	TSL:2	c.444+4047C>T		intron	N/A	ENSP00000373355.5

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55335 AN: 151950 Hom.: 10199 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.364 AC: 55398 AN: 152068 Hom.: 10218 Cov.: 32 AF XY: 0.358 AC XY: 26620 AN XY: 74296

African (AFR) AF: 0.367 AC: 15236 AN: 41460

American (AMR) AF: 0.349 AC: 5333 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3472

East Asian (EAS) AF: 0.211 AC: 1094 AN: 5174

South Asian (SAS) AF: 0.227 AC: 1096 AN: 4826

European-Finnish (FIN) AF: 0.373 AC: 3931 AN: 10546

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26420 AN: 67980

Other (OTH) AF: 0.347 AC: 733 AN: 2112

Alfa AF: 0.378 Hom.: 44642

Bravo AF: 0.369

Asia WGS AF: 0.244 AC: 846 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	1.2
DANN	Benign	0.27
PhyloP100		0.11
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: rs711635; hg19: chr3-4490513;