chr3-4198269-A-C

Variant names:

• chr3-4198269-A-C
• rs1444056
• ENST00000448413.5:n.1015-129524T>G

Variant summary

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

The ENST00000448413.5(SUMF1):​n.1015-129524T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,880 control chromosomes in the GnomAD database, including 7,839 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 (7839 hom., cov: 31)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMF1	XM_011533624.4	c.1015-129524T>G		intron_variant	Intron 8 of 9		XP_011531926.1
SUMF1	XM_017006252.3	c.955-129524T>G		intron_variant	Intron 7 of 8		XP_016861741.1
SUMF1	XM_017006253.2	c.940-129524T>G		intron_variant	Intron 7 of 8		XP_016861742.1
SUMF1	XM_017006254.3	c.1015-129524T>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.1015-129524T>G		intron_variant	Intron 8 of 12	2		ENSP00000404384.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48377 AN: 151764 Hom.: 7815 Cov.: 31

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.319 AC: 48452 AN: 151880 Hom.: 7839 Cov.: 31 AF XY: 0.323 AC XY: 23971 AN XY: 74200

African (AFR) AF: 0.285 AC: 11790 AN: 41438

American (AMR) AF: 0.337 AC: 5135 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3466

East Asian (EAS) AF: 0.402 AC: 2064 AN: 5134

South Asian (SAS) AF: 0.293 AC: 1409 AN: 4816

European-Finnish (FIN) AF: 0.403 AC: 4247 AN: 10544

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21657 AN: 67932

Other (OTH) AF: 0.330 AC: 697 AN: 2110

Alfa AF: 0.316 Hom.: 4109

Bravo AF: 0.315

Asia WGS AF: 0.370 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.62
PhyloP100		-0.46
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: rs1444056; hg19: chr3-4239953;