rs2633851

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182760.4(SUMF1):c.*11A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,611,076 control chromosomes in the GnomAD database, including 276,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31464 hom., cov: 33)

Exomes 𝑓: 0.57 ( 245449 hom. )

Consequence

SUMF1
NM_182760.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.812

Publications

16 publications found

Variant links:

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

SUMF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 3-4362133-T-A is Benign according to our data. Variant chr3-4362133-T-A is described in ClinVar as Benign. ClinVar VariationId is 96558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMF1	NM_182760.4 link	c.*11A>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000272902.10	NP_877437.2	Q8NBK3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000272902.10 link	c.*11A>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_182760.4	ENSP00000272902.5		Q8NBK3-1

Frequencies

GnomAD3 genomes

AF:

0.635

AC:

96440

AN:

151888

Hom.:

31421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.758

Gnomad AMI

AF:

0.603

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.619

Gnomad EAS

AF:

0.757

Gnomad SAS

AF:

0.751

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.641

GnomAD2 exomes

AF:

0.634

AC:

158118

AN:

249370

AF XY:

0.631

show subpopulations

Gnomad AFR exome

AF:

0.770

Gnomad AMR exome

AF:

0.738

Gnomad ASJ exome

AF:

0.600

Gnomad EAS exome

AF:

0.764

Gnomad FIN exome

AF:

0.576

Gnomad NFE exome

AF:

0.550

Gnomad OTH exome

AF:

0.605

GnomAD4 exome

AF:

0.575

AC:

838431

AN:

1459070

Hom.:

245449

Cov.:

AF XY:

0.578

AC XY:

419951

AN XY:

725950

show subpopulations

African (AFR)

AF:

0.769

AC:

25723

AN:

33444

American (AMR)

AF:

0.725

AC:

32399

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.595

AC:

15547

AN:

26110

East Asian (EAS)

AF:

0.773

AC:

30663

AN:

39666

South Asian (SAS)

AF:

0.735

AC:

63360

AN:

86192

European-Finnish (FIN)

AF:

0.574

AC:

30622

AN:

53350

Middle Eastern (MID)

AF:

0.628

AC:

3517

AN:

5604

European-Non Finnish (NFE)

AF:

0.541

AC:

600693

AN:

1109732

Other (OTH)

AF:

0.596

AC:

35907

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

16815

33629

50444

67258

84073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17252

34504

51756

69008

86260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.635

AC:

96534

AN:

152006

Hom.:

31464

Cov.:

AF XY:

0.641

AC XY:

47628

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.758

AC:

31461

AN:

41516

American (AMR)

AF:

0.678

AC:

10356

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

2144

AN:

3466

East Asian (EAS)

AF:

0.758

AC:

3905

AN:

5154

South Asian (SAS)

AF:

0.751

AC:

3623

AN:

4824

European-Finnish (FIN)

AF:

0.582

AC:

6137

AN:

10550

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.542

AC:

36819

AN:

67908

Other (OTH)

AF:

0.645

AC:

1362

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1781

3562

5343

7124

8905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.497

Hom.:

2497

Bravo

AF:

0.649

Asia WGS

AF:

0.770

AC:

2679

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 26, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 15, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Multiple sulfatase deficiency

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 15, 2021

Genome-Nilou Lab

Significance: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

-0.79

CADD

Benign

7.4

(source)

DANN

Benign

0.58

PhyloP100

0.81

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over