rs3846149

Variant names:

• chr3-4103729-A-G
• rs3846149
• ENST00000448413.5:n.1015-34984T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-4103729-A-G
• chr3-4103729-A-T

Variant summary

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

The ENST00000448413.5(SUMF1):​n.1015-34984T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,166 control chromosomes in the GnomAD database, including 1,763 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 0.11 (1763 hom., cov: 32)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMF1	XM_011533624.4	c.1015-34984T>C		intron_variant	Intron 8 of 9		XP_011531926.1
SUMF1	XM_017006252.3	c.955-34984T>C		intron_variant	Intron 7 of 8		XP_016861741.1
SUMF1	XM_017006253.2	c.940-34984T>C		intron_variant	Intron 7 of 8		XP_016861742.1
SUMF1	XM_017006254.3	c.1015-34984T>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.1015-34984T>C		intron_variant	Intron 8 of 12	2		ENSP00000404384.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16445 AN: 152048 Hom.: 1747 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0152

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0290

Gnomad OTH AF: 0.0870

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

GnomAD4 genome AF: 0.108 AC: 16493 AN: 152166 Hom.: 1763 Cov.: 32 AF XY: 0.107 AC XY: 7993 AN XY: 74382

African (AFR) AF: 0.254 AC: 10514 AN: 41450

American (AMR) AF: 0.145 AC: 2221 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.155 AC: 804 AN: 5172

South Asian (SAS) AF: 0.119 AC: 572 AN: 4818

European-Finnish (FIN) AF: 0.0152 AC: 162 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0290 AC: 1976 AN: 68024

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.0307 Hom.: 46

Bravo AF: 0.127

Asia WGS AF: 0.138 AC: 480 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	2.3
DANN	Benign	0.64
PhyloP100		-0.26
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: rs3846149; hg19: chr3-4145413;