rs10510280

Variant names:

• chr3-3924226-G-C
• rs10510280
• ENST00000448413.5:n.1192-96717C>G

Variant summary

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

The ENST00000448413.5(SUMF1):​n.1192-96717C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 151,924 control chromosomes in the GnomAD database, including 201 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 0.042 (201 hom., cov: 32)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894
• Publications: 1 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

ENSG00000287720 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000448413.5	n.1192-96717C>G		intron_variant	Intron 9 of 12	2		ENSP00000404384.1
ENSG00000287720	ENST00000661097.1	n.130+5388G>C		intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6398 AN: 151806 Hom.: 202 Cov.: 32

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0490

Gnomad SAS AF: 0.0976

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.0459

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

GnomAD4 genome AF: 0.0421 AC: 6397 AN: 151924 Hom.: 201 Cov.: 32 AF XY: 0.0425 AC XY: 3156 AN XY: 74258

African (AFR) AF: 0.0100 AC: 415 AN: 41518

American (AMR) AF: 0.0439 AC: 668 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 425 AN: 3468

East Asian (EAS) AF: 0.0493 AC: 253 AN: 5132

South Asian (SAS) AF: 0.0977 AC: 470 AN: 4812

European-Finnish (FIN) AF: 0.0300 AC: 318 AN: 10600

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0548 AC: 3717 AN: 67848

Other (OTH) AF: 0.0450 AC: 95 AN: 2112

Alfa AF: 0.0456 Hom.: 27

Bravo AF: 0.0405

Asia WGS AF: 0.0730 AC: 252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.77
PhyloP100		0.89
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: rs10510280; hg19: chr3-3965910;