3-3871262-C-G

Variant names:

• chr3-3871262-C-G
• rs1352405
• ENST00000448413.5:n.1192-43753G>C

Variant summary

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

The ENST00000448413.5(SUMF1):​n.1192-43753G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 152,076 control chromosomes in the GnomAD database, including 54,590 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 0.81 (54590 hom., cov: 31)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• 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: ClinGen, Orphanet, PanelApp Australia, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.982 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUMF1	ENST00000448413.5	TSL:2	n.1192-43753G>C		intron	N/A	ENSP00000404384.1	F5GXA0

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122766 AN: 151958 Hom.: 54594 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.967

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.928

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.988

Gnomad OTH AF: 0.844

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

GnomAD4 genome AF: 0.807 AC: 122778 AN: 152076 Hom.: 54590 Cov.: 31 AF XY: 0.812 AC XY: 60357 AN XY: 74360

African (AFR) AF: 0.398 AC: 16483 AN: 41398

American (AMR) AF: 0.879 AC: 13415 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.967 AC: 3356 AN: 3470

East Asian (EAS) AF: 0.828 AC: 4287 AN: 5176

South Asian (SAS) AF: 0.928 AC: 4471 AN: 4818

European-Finnish (FIN) AF: 1.00 AC: 10617 AN: 10620

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.988 AC: 67212 AN: 68010

Other (OTH) AF: 0.836 AC: 1765 AN: 2110

Alfa AF: 0.843 Hom.: 3402

Bravo AF: 0.777

Asia WGS AF: 0.838 AC: 2915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.23
PhyloP100		0.035
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1352405;

hg19: chr3-3912946;