rs793396

Positions:

• chr3-4452187-G-A
• chr3-4452187-G-T

Variant summary

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

The NM_182760.4(SUMF1):​c.444+689C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 150,536 control chromosomes in the GnomAD database, including 4,264 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 0.22 (4264 hom., cov: 31)
• Consequence: SUMF1 NM_182760.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUMF1	NM_182760.4	c.444+689C>T		intron_variant		ENST00000272902.10	NP_877437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000272902.10	c.444+689C>T		intron_variant		1	NM_182760.4	ENSP00000272902.5

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33256 AN: 150488 Hom.: 4267 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.00407

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.221 AC: 33255 AN: 150536 Hom.: 4264 Cov.: 31 AF XY: 0.216 AC XY: 15887 AN XY: 73438

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.00427

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.205

Alfa AF: 0.243 Hom.: 2144

Bravo AF: 0.213

Asia WGS AF: 0.0620 AC: 215 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.67

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: rs793396; hg19: chr3-4493871;