Variant 3-4449362-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.303

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 links:

SUMF1 (HGNC:):

SUMF1 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
SUMF1	NM_182760.4 linkuse as main transcript	c.445-22T>C		intron_variant		ENST00000272902.10	NP_877437.2	Q8NBK3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000272902.10 linkuse as main transcript	c.445-22T>C		intron_variant		1	NM_182760.4	ENSP00000272902.5		Q8NBK3-1

Frequencies

GnomAD3 genomes

AF:

0.0323

AC:

4915

AN:

152194

Hom.:

113

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0443

AC XY:

32232

AN XY:

726780

show subpopulations

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.:

AF XY:

0.0307

AC XY:

2290

AN XY:

74486

show subpopulations

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.:

Bravo

AF:

0.0316

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 01, 2018	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 23, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over