rs35083095

chr3-4362134-T-Cchr3-4362134-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.18

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 96557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-4362134-T-C is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
SUMF1	NM_182760.4	c.*10A>G		3_prime_UTR_variant	9/9	ENST00000272902.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUMF1	ENST00000272902.10	c.*10A>G		3_prime_UTR_variant	9/9	1	NM_182760.4	P1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65440 AN: 151908 Hom.: 15383 Cov.: 34

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

GnomAD3 exomes AF: 0.503 AC: 125370 AN: 249268 Hom.: 32613 AF XY: 0.503 AC XY: 67814 AN XY: 134820

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 SAS exome AF: 0.471

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.: 35 AF XY: 0.493 AC XY: 358050 AN XY: 726188

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.587

Gnomad4 ASJ exome AF: 0.526

Gnomad4 EAS exome AF: 0.625

Gnomad4 SAS exome AF: 0.475

Gnomad4 FIN exome AF: 0.519

Gnomad4 NFE exome AF: 0.493

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.431 AC: 65465 AN: 152028 Hom.: 15387 Cov.: 34 AF XY: 0.435 AC XY: 32356 AN XY: 74312

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.473

Alfa AF: 0.453 Hom.: 6081

Bravo AF: 0.428

Asia WGS AF: 0.506 AC: 1759 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 26, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Multiple sulfatase deficiency Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 18, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.0
Dann	Benign	0.39

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

Other links and lift over

dbSNP: rs35083095; hg19: chr3-4403818; COSMIC: COSV55991862;