3-4103345-A-C

Variant names:

• chr3-4103345-A-C
• rs10510286
• XM_011533624.4:c.1015-34600T>G

Variant summary

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

The ENST00000448413.5(SUMF1):​n.1015-34600T>G 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 152,076 control chromosomes in the GnomAD database, including 3,718 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 (3718 hom., cov: 32)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• 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: 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 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.1015-34600T>G		intron	N/A	ENSP00000404384.1	F5GXA0

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22823 AN: 151958 Hom.: 3694 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: 0.156

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0154

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.151 AC: 22895 AN: 152076 Hom.: 3718 Cov.: 32 AF XY: 0.149 AC XY: 11090 AN XY: 74328

African (AFR) AF: 0.395 AC: 16347 AN: 41420

American (AMR) AF: 0.172 AC: 2621 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3468

East Asian (EAS) AF: 0.156 AC: 808 AN: 5174

South Asian (SAS) AF: 0.123 AC: 592 AN: 4800

European-Finnish (FIN) AF: 0.0154 AC: 163 AN: 10602

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0301 AC: 2045 AN: 68018

Other (OTH) AF: 0.120 AC: 254 AN: 2110

Alfa AF: 0.109 Hom.: 326

Bravo AF: 0.175

Asia WGS AF: 0.153 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.11
DANN	Benign	0.57
PhyloP100		-2.0
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: rs10510286;

hg19: chr3-4145029;