rs1596472

Variant names:

• chr3-4121878-G-A
• rs1596472
• XM_011533624.4:c.1015-53133C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-4121878-G-A
• chr3-4121878-G-C

Variant summary

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

The ENST00000448413.5(SUMF1):​n.1015-53133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 151,776 control chromosomes in the GnomAD database, including 2,437 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 0.16 (2437 hom., cov: 32)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 3 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=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 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.1015-53133C>T		intron	N/A	ENSP00000404384.1	F5GXA0

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24000 AN: 151658 Hom.: 2433 Cov.: 32

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.158 AC: 24011 AN: 151776 Hom.: 2437 Cov.: 32 AF XY: 0.158 AC XY: 11744 AN XY: 74192

African (AFR) AF: 0.0421 AC: 1742 AN: 41398

American (AMR) AF: 0.173 AC: 2635 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 477 AN: 3468

East Asian (EAS) AF: 0.112 AC: 580 AN: 5166

South Asian (SAS) AF: 0.0979 AC: 468 AN: 4782

European-Finnish (FIN) AF: 0.254 AC: 2666 AN: 10514

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14966 AN: 67890

Other (OTH) AF: 0.149 AC: 314 AN: 2104

Alfa AF: 0.184 Hom.: 378

Bravo AF: 0.147

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.54
DANN	Benign	0.39
PhyloP100		-1.2
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: rs1596472;

hg19: chr3-4163562;