XM_011533624.4:c.1015-25468G>A

Variant names:

• chr3-4094213-C-T
• rs10510283
• XM_011533624.4:c.1015-25468G>A

Variant summary

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

The XM_011533624.4(SUMF1):​c.1015-25468G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 151,988 control chromosomes in the GnomAD database, including 1,463 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 0.10 (1463 hom., cov: 32)
• Consequence: SUMF1 XM_011533624.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 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.1015-25468G>A		intron	N/A	ENSP00000404384.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15371 AN: 151872 Hom.: 1451 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0154

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0875

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

GnomAD4 genome AF: 0.101 AC: 15416 AN: 151988 Hom.: 1463 Cov.: 32 AF XY: 0.101 AC XY: 7466 AN XY: 74284

African (AFR) AF: 0.228 AC: 9435 AN: 41394

American (AMR) AF: 0.144 AC: 2204 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 47 AN: 3468

East Asian (EAS) AF: 0.158 AC: 814 AN: 5164

South Asian (SAS) AF: 0.120 AC: 577 AN: 4800

European-Finnish (FIN) AF: 0.0154 AC: 163 AN: 10596

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

European-Non Finnish (NFE) AF: 0.0291 AC: 1977 AN: 67984

Other (OTH) AF: 0.0870 AC: 184 AN: 2114

Alfa AF: 0.0692 Hom.: 112

Bravo AF: 0.119

Asia WGS AF: 0.143 AC: 498 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	2.3
DANN	Benign	0.71
PhyloP100		-0.21
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: rs10510283; hg19: chr3-4135897;