rs794185

Positions:

• chr3-4395674-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182760.4(SUMF1):​c.954+15191A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,074 control chromosomes in the GnomAD database, including 14,975 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 0.44 (14975 hom., cov: 32)
• Consequence: SUMF1 NM_182760.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUMF1	NM_182760.4	c.954+15191A>G		intron_variant		ENST00000272902.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUMF1	ENST00000272902.10	c.954+15191A>G		intron_variant		1	NM_182760.4	P1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66799 AN: 151956 Hom.: 14964 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.399

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.440 AC: 66867 AN: 152074 Hom.: 14975 Cov.: 32 AF XY: 0.434 AC XY: 32280 AN XY: 74310

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.397

Alfa AF: 0.421 Hom.: 31666

Bravo AF: 0.451

Asia WGS AF: 0.297 AC: 1032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.29

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: rs794185; hg19: chr3-4437358; COSMIC: COSV55994075;