rs3852047

Variant names:

• chr3-4403105-G-A
• rs3852047
• NM_182760.4:c.954+7760C>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.954+7760C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 152,236 control chromosomes in the GnomAD database, including 106 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 0.029 (106 hom., cov: 32)
• Consequence: SUMF1 NM_182760.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0637 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.954+7760C>T		intron	N/A	NP_877437.2
	SUMF1	NM_001164675.2		c.954+7760C>T		intron	N/A	NP_001158147.1	Q8NBK3-5
	SUMF1	NM_001164674.2		c.879+7760C>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.954+7760C>T		intron	N/A	ENSP00000272902.5	Q8NBK3-1
	SUMF1	ENST00000405420.2	TSL:1	c.954+7760C>T		intron	N/A	ENSP00000384977.2	Q8NBK3-5
	SUMF1	ENST00000948922.1		c.975+7760C>T		intron	N/A	ENSP00000618981.1

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4453 AN: 152118 Hom.: 106 Cov.: 32

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00746

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0293 AC: 4459 AN: 152236 Hom.: 106 Cov.: 32 AF XY: 0.0290 AC XY: 2158 AN XY: 74434

African (AFR) AF: 0.0657 AC: 2730 AN: 41528

American (AMR) AF: 0.0272 AC: 416 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00779 AC: 27 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00747 AC: 36 AN: 4822

European-Finnish (FIN) AF: 0.0203 AC: 215 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0138 AC: 936 AN: 68016

Other (OTH) AF: 0.0260 AC: 55 AN: 2114

Alfa AF: 0.0167 Hom.: 16

Bravo AF: 0.0324

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.71
PhyloP100		0.55
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: rs3852047; hg19: chr3-4444789;