rs711634

Positions:

• chr3-4449362-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_182760.4(SUMF1):​c.445-22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 1,613,000 control chromosomes in the GnomAD database, including 1,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (113 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1762 hom.)
• Consequence: SUMF1 NM_182760.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.303

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 3-4449362-A-G is Benign according to our data. Variant chr3-4449362-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 263007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUMF1	NM_182760.4	c.445-22T>C		intron_variant		ENST00000272902.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUMF1	ENST00000272902.10	c.445-22T>C		intron_variant		1	NM_182760.4	P1

Frequencies

GnomAD3 genomes AF: 0.0323 AC: 4915 AN: 152194 Hom.: 113 Cov.: 32

Gnomad AFR AF: 0.00970

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.0505

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00911

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0502

Gnomad OTH AF: 0.0301

GnomAD3 exomes AF: 0.0313 AC: 7870 AN: 251198 Hom.: 188 AF XY: 0.0319 AC XY: 4327 AN XY: 135790

Gnomad AFR exome AF: 0.00794

Gnomad AMR exome AF: 0.0139

Gnomad ASJ exome AF: 0.0453

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00836

Gnomad FIN exome AF: 0.0345

Gnomad NFE exome AF: 0.0493

Gnomad OTH exome AF: 0.0328

GnomAD4 exome AF: 0.0455 AC: 66462 AN: 1460688 Hom.: 1762 Cov.: 30 AF XY: 0.0443 AC XY: 32232 AN XY: 726780

Gnomad4 AFR exome AF: 0.00661

Gnomad4 AMR exome AF: 0.0147

Gnomad4 ASJ exome AF: 0.0463

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00820

Gnomad4 FIN exome AF: 0.0360

Gnomad4 NFE exome AF: 0.0534

Gnomad4 OTH exome AF: 0.0391

GnomAD4 genome AF: 0.0323 AC: 4917 AN: 152312 Hom.: 113 Cov.: 32 AF XY: 0.0307 AC XY: 2290 AN XY: 74486

Gnomad4 AFR AF: 0.00967

Gnomad4 AMR AF: 0.0247

Gnomad4 ASJ AF: 0.0505

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00953

Gnomad4 FIN AF: 0.0336

Gnomad4 NFE AF: 0.0502

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0417 Hom.: 62

Bravo AF: 0.0316

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 23, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 01, 2018	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs711634; hg19: chr3-4491046;