Genetic Variant SUMF1:n.*1784T>C (chr3-3781421-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000448413.5(SUMF1):n.*1784T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 149,616 control chromosomes in the GnomAD database, including 17,578 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 17576 hom., cov: 27)

Exomes 𝑓: 0.28 ( 2 hom. )

Consequence

SUMF1
ENST00000448413.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.90

Publications

2 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: ClinGen, Orphanet, PanelApp Australia, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)

SUMF1 links:

LOC100130207 (HGNC:):

LOC100130207 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000448413.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.04).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000448413.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100130207	NR_149025.1		n.535+1082T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SUMF1	ENST00000448413.5	TSL:2	n.*1784T>C	non_coding_transcript_exon	Exon 13 of 13	ENSP00000404384.1	F5GXA0
SUMF1	ENST00000448413.5	TSL:2	n.*1784T>C	3_prime_UTR	Exon 13 of 13	ENSP00000404384.1	F5GXA0
SUMF1	ENST00000470751.5	TSL:2	n.535+1082T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

68960

AN:

149446

Hom.:

17582

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.479

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.532

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.561

Gnomad NFE

AF:

0.588

Gnomad OTH

AF:

0.484

GnomAD4 exome

AF:

0.276

AC:

AN:

Hom.:

Cov.:

AF XY:

0.238

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.341

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.461

AC:

68953

AN:

149558

Hom.:

17576

Cov.:

AF XY:

0.459

AC XY:

33516

AN XY:

73026

show subpopulations

African (AFR)

AF:

0.244

AC:

9865

AN:

40436

American (AMR)

AF:

0.468

AC:

7015

AN:

14994

Ashkenazi Jewish (ASJ)

AF:

0.532

AC:

1830

AN:

3440

East Asian (EAS)

AF:

0.240

AC:

1207

AN:

5028

South Asian (SAS)

AF:

0.421

AC:

1983

AN:

4706

European-Finnish (FIN)

AF:

0.569

AC:

5811

AN:

10208

Middle Eastern (MID)

AF:

0.566

AC:

163

AN:

288

European-Non Finnish (NFE)

AF:

0.588

AC:

39656

AN:

67494

Other (OTH)

AF:

0.481

AC:

992

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1680

3359

5039

6718

8398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<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:

0.503

Hom.:

2411

Bravo

AF:

0.444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.0

(source)

DANN

Benign

0.34

PhyloP100

-2.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over