rs2587949

Variant names:

• chr3-4181932-C-G
• rs2587949
• ENST00000448413.5:n.1015-113187G>C

Variant summary

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

The ENST00000448413.5(SUMF1):​n.1015-113187G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,038 control chromosomes in the GnomAD database, including 17,439 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 0.48 (17439 hom., cov: 32)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMF1	XM_011533624.4	c.1015-113187G>C		intron_variant	Intron 8 of 9		XP_011531926.1
SUMF1	XM_017006252.3	c.955-113187G>C		intron_variant	Intron 7 of 8		XP_016861741.1
SUMF1	XM_017006253.2	c.940-113187G>C		intron_variant	Intron 7 of 8		XP_016861742.1
SUMF1	XM_017006254.3	c.1015-113187G>C		intron_variant	Intron 8 of 9		XP_016861743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000448413.5	n.1015-113187G>C		intron_variant	Intron 8 of 12	2		ENSP00000404384.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72305 AN: 151918 Hom.: 17395 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.476 AC: 72409 AN: 152038 Hom.: 17439 Cov.: 32 AF XY: 0.479 AC XY: 35548 AN XY: 74290

African (AFR) AF: 0.510 AC: 21164 AN: 41490

American (AMR) AF: 0.519 AC: 7924 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1541 AN: 3468

East Asian (EAS) AF: 0.582 AC: 3001 AN: 5160

South Asian (SAS) AF: 0.434 AC: 2089 AN: 4814

European-Finnish (FIN) AF: 0.493 AC: 5209 AN: 10556

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29857 AN: 67956

Other (OTH) AF: 0.465 AC: 982 AN: 2110

Alfa AF: 0.462 Hom.: 2026

Bravo AF: 0.485

Asia WGS AF: 0.518 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.79
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2587949; hg19: chr3-4223616;