3-4143440-T-C

Variant names:

• chr3-4143440-T-C
• rs1843303
• ENST00000448413.5:n.1015-74695A>G

Variant summary

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

The ENST00000448413.5(SUMF1):​n.1015-74695A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,862 control chromosomes in the GnomAD database, including 8,412 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 0.32 (8412 hom., cov: 32)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMF1	XM_011533624.4	c.1015-74695A>G		intron_variant	Intron 8 of 9		XP_011531926.1
SUMF1	XM_017006252.3	c.955-74695A>G		intron_variant	Intron 7 of 8		XP_016861741.1
SUMF1	XM_017006253.2	c.940-74695A>G		intron_variant	Intron 7 of 8		XP_016861742.1
SUMF1	XM_017006254.3	c.1015-74695A>G		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.1015-74695A>G		intron_variant	Intron 8 of 12	2		ENSP00000404384.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49158 AN: 151744 Hom.: 8386 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.324 AC: 49216 AN: 151862 Hom.: 8412 Cov.: 32 AF XY: 0.330 AC XY: 24524 AN XY: 74242

African (AFR) AF: 0.294 AC: 12174 AN: 41392

American (AMR) AF: 0.419 AC: 6392 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1062 AN: 3470

East Asian (EAS) AF: 0.571 AC: 2943 AN: 5150

South Asian (SAS) AF: 0.380 AC: 1829 AN: 4812

European-Finnish (FIN) AF: 0.373 AC: 3931 AN: 10552

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19958 AN: 67910

Other (OTH) AF: 0.320 AC: 672 AN: 2100

Alfa AF: 0.166 Hom.: 333

Bravo AF: 0.331

Asia WGS AF: 0.442 AC: 1537 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.85
DANN	Benign	0.41
PhyloP100		-0.62
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: rs1843303; hg19: chr3-4185124;