rs317575

Variant names:

• chr3-4047125-C-T
• rs317575
• ENST00000448413.5:n.1191+21444G>A

Variant summary

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

The ENST00000448413.5(SUMF1):​n.1191+21444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,996 control chromosomes in the GnomAD database, including 6,275 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 0.22 (6275 hom., cov: 32)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• 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: 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMF1	XM_017006254.3	c.1192-12379G>A		intron_variant	Intron 9 of 9		XP_016861743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000448413.5	n.1191+21444G>A		intron_variant	Intron 9 of 12	2		ENSP00000404384.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33533 AN: 151876 Hom.: 6253 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.0771

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.221 AC: 33612 AN: 151996 Hom.: 6275 Cov.: 32 AF XY: 0.215 AC XY: 15999 AN XY: 74294

African (AFR) AF: 0.511 AC: 21166 AN: 41388

American (AMR) AF: 0.136 AC: 2068 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3472

East Asian (EAS) AF: 0.00502 AC: 26 AN: 5176

South Asian (SAS) AF: 0.0765 AC: 369 AN: 4824

European-Finnish (FIN) AF: 0.104 AC: 1103 AN: 10592

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7874 AN: 67964

Other (OTH) AF: 0.197 AC: 416 AN: 2112

Alfa AF: 0.182 Hom.: 725

Bravo AF: 0.238

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.55
DANN	Benign	0.74
PhyloP100		-0.36
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: rs317575; hg19: chr3-4088809;