rs711634

Variant names:

• chr3-4449362-A-G
• rs711634
• NM_182760.4:c.445-22T>C

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: 0.303
• 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: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SUMF1	NM_182760.4	c.445-22T>C		intron_variant	Intron 2 of 8	ENST00000272902.10	NP_877437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000272902.10	c.445-22T>C		intron_variant	Intron 2 of 8	1	NM_182760.4	ENSP00000272902.5

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

GnomAD2 exomes AF: 0.0313 AC: 7870 AN: 251198 AF XY: 0.0319

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 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

African (AFR) AF: 0.00661 AC: 221 AN: 33428

American (AMR) AF: 0.0147 AC: 659 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0463 AC: 1210 AN: 26122

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39686

South Asian (SAS) AF: 0.00820 AC: 707 AN: 86234

European-Finnish (FIN) AF: 0.0360 AC: 1925 AN: 53410

Middle Eastern (MID) AF: 0.0116 AC: 67 AN: 5766

European-Non Finnish (NFE) AF: 0.0534 AC: 59313 AN: 1110966

Other (OTH) AF: 0.0391 AC: 2359 AN: 60356

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

African (AFR) AF: 0.00967 AC: 402 AN: 41562

American (AMR) AF: 0.0247 AC: 378 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0505 AC: 175 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00953 AC: 46 AN: 4826

European-Finnish (FIN) AF: 0.0336 AC: 357 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0502 AC: 3417 AN: 68018

Other (OTH) AF: 0.0298 AC: 63 AN: 2116

Alfa AF: 0.0416 Hom.: 76

Bravo AF: 0.0316

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Dec 01, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 23, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		0.30
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs711634; hg19: chr3-4491046;