rs35083095

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.*10A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,611,632 control chromosomes in the GnomAD database, including 195,194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15387 hom., cov: 34)

Exomes 𝑓: 0.49 ( 179807 hom. )

Consequence

SUMF1
NM_182760.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.18

Publications

18 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=-0.83).

BP6

Variant 3-4362134-T-C is Benign according to our data. Variant chr3-4362134-T-C is described in ClinVar as Benign. ClinVar VariationId is 96557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

65440

AN:

151908

Hom.:

15383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.588

Gnomad AMR

AF:

0.527

Gnomad ASJ

AF:

0.546

Gnomad EAS

AF:

0.613

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.524

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.492

Gnomad OTH

AF:

0.473

GnomAD2 exomes

AF:

0.503

AC:

125370

AN:

249268

AF XY:

0.503

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.601

Gnomad ASJ exome

AF:

0.533

Gnomad EAS exome

AF:

0.626

Gnomad FIN exome

AF:

0.518

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.507

GnomAD4 exome

AF:

0.493

AC:

719494

AN:

1459604

Hom.:

179807

Cov.:

AF XY:

0.493

AC XY:

358050

AN XY:

726188

show subpopulations

African (AFR)

AF:

0.216

AC:

7226

AN:

33454

American (AMR)

AF:

0.587

AC:

26226

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.526

AC:

13740

AN:

26116

East Asian (EAS)

AF:

0.625

AC:

24784

AN:

39666

South Asian (SAS)

AF:

0.475

AC:

40975

AN:

86196

European-Finnish (FIN)

AF:

0.519

AC:

27706

AN:

53346

Middle Eastern (MID)

AF:

0.492

AC:

2759

AN:

5610

European-Non Finnish (NFE)

AF:

0.493

AC:

546951

AN:

1110216

Other (OTH)

AF:

0.483

AC:

29127

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

16853

33705

50558

67410

84263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16038

32076

48114

64152

80190

<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:

0.431

AC:

65465

AN:

152028

Hom.:

15387

Cov.:

AF XY:

0.435

AC XY:

32356

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.227

AC:

9417

AN:

41524

American (AMR)

AF:

0.527

AC:

8061

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

1894

AN:

3468

East Asian (EAS)

AF:

0.614

AC:

3163

AN:

5152

South Asian (SAS)

AF:

0.476

AC:

2294

AN:

4822

European-Finnish (FIN)

AF:

0.524

AC:

5522

AN:

10548

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.492

AC:

33445

AN:

67920

Other (OTH)

AF:

0.473

AC:

999

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1839

3678

5518

7357

9196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<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:

0.459

Hom.:

8549

Bravo

AF:

0.428

Asia WGS

AF:

0.506

AC:

1759

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

Apr 26, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Multiple sulfatase deficiency

Benign:3

Nov 18, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.0

(source)

DANN

Benign

0.39

PhyloP100

-1.2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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