3-4143695-T-C

Variant names:

• chr3-4143695-T-C
• rs2587916
• ENST00000448413.5:n.1015-74950A>G

Variant summary

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

The ENST00000448413.5(SUMF1):​n.1015-74950A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,042 control chromosomes in the GnomAD database, including 5,174 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 0.24 (5174 hom., cov: 32)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000448413.5. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF1	ENST00000448413.5	TSL:2	n.1015-74950A>G		intron	N/A	ENSP00000404384.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36560 AN: 151924 Hom.: 5169 Cov.: 32

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.241 AC: 36586 AN: 152042 Hom.: 5174 Cov.: 32 AF XY: 0.245 AC XY: 18176 AN XY: 74300

African (AFR) AF: 0.0930 AC: 3859 AN: 41494

American (AMR) AF: 0.248 AC: 3791 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1060 AN: 3472

East Asian (EAS) AF: 0.396 AC: 2043 AN: 5158

South Asian (SAS) AF: 0.260 AC: 1255 AN: 4822

European-Finnish (FIN) AF: 0.372 AC: 3928 AN: 10558

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19842 AN: 67964

Other (OTH) AF: 0.263 AC: 555 AN: 2112

Alfa AF: 0.150 Hom.: 323

Bravo AF: 0.229

Asia WGS AF: 0.306 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.83
PhyloP100		-0.69
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: rs2587916; hg19: chr3-4185379;