rs317575

chr3-4047125-C-T

Variant summary

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

The XM_017006254.3(SUMF1):c.1192-12379G>A 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 151,996 control chromosomes in the GnomAD database, including 6,275 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 (6275 hom., cov: 32)
• Consequence: SUMF1 XM_017006254.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUMF1	XM_017006254.3	c.1192-12379G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUMF1	ENST00000448413.5	c.1191+21444G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33533 AN: 151876 Hom.: 6253 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.0771

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.221 AC: 33612 AN: 151996 Hom.: 6275 Cov.: 32 AF XY: 0.215 AC XY: 15999 AN XY: 74294

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.00502

Gnomad4 SAS AF: 0.0765

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.197

Alfa AF: 0.173 Hom.: 641

Bravo AF: 0.238

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.55
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs317575; hg19: chr3-4088809;