3-4102694-C-T

Variant names:

• chr3-4102694-C-T
• rs10510285
• ENST00000448413.5:n.1015-33949G>A

Variant summary

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

The ENST00000448413.5(SUMF1):​n.1015-33949G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,964 control chromosomes in the GnomAD database, including 3,706 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 0.15 (3706 hom., cov: 32)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMF1	XM_011533624.4	c.1015-33949G>A		intron_variant	Intron 8 of 9		XP_011531926.1
SUMF1	XM_017006252.3	c.955-33949G>A		intron_variant	Intron 7 of 8		XP_016861741.1
SUMF1	XM_017006253.2	c.940-33949G>A		intron_variant	Intron 7 of 8		XP_016861742.1
SUMF1	XM_017006254.3	c.1015-33949G>A		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.1015-33949G>A		intron_variant	Intron 8 of 12	2		ENSP00000404384.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22801 AN: 151846 Hom.: 3682 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0152

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.151 AC: 22873 AN: 151964 Hom.: 3706 Cov.: 32 AF XY: 0.149 AC XY: 11071 AN XY: 74268

African (AFR) AF: 0.395 AC: 16328 AN: 41342

American (AMR) AF: 0.172 AC: 2622 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3472

East Asian (EAS) AF: 0.155 AC: 805 AN: 5180

South Asian (SAS) AF: 0.123 AC: 592 AN: 4796

European-Finnish (FIN) AF: 0.0152 AC: 161 AN: 10596

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0301 AC: 2044 AN: 67998

Other (OTH) AF: 0.121 AC: 255 AN: 2112

Alfa AF: 0.0307 Hom.: 77

Bravo AF: 0.175

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.49
DANN	Benign	0.37
PhyloP100		-0.46
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: rs10510285; hg19: chr3-4144378;