3-4163939-G-A

Variant names:

• chr3-4163939-G-A
• rs1351950
• XM_011533624.4:c.1015-95194C>T

Variant summary

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

The ENST00000448413.5(SUMF1):​n.1015-95194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,980 control chromosomes in the GnomAD database, including 5,963 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 0.27 (5963 hom., cov: 31)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 11 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 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.1015-95194C>T		intron	N/A	ENSP00000404384.1	F5GXA0

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41470 AN: 151862 Hom.: 5964 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.273 AC: 41470 AN: 151980 Hom.: 5963 Cov.: 31 AF XY: 0.268 AC XY: 19936 AN XY: 74308

African (AFR) AF: 0.199 AC: 8235 AN: 41440

American (AMR) AF: 0.287 AC: 4387 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1210 AN: 3464

East Asian (EAS) AF: 0.183 AC: 946 AN: 5178

South Asian (SAS) AF: 0.229 AC: 1099 AN: 4804

European-Finnish (FIN) AF: 0.243 AC: 2572 AN: 10578

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.323 AC: 21923 AN: 67928

Other (OTH) AF: 0.302 AC: 637 AN: 2110

Alfa AF: 0.305 Hom.: 31664

Bravo AF: 0.272

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.77
PhyloP100		0.0040
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: rs1351950;

hg19: chr3-4205623;