rs1444056

Positions:

• chr3-4198269-A-C

Variant summary

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

The XM_011533624.4(SUMF1):​c.1015-129524T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,880 control chromosomes in the GnomAD database, including 7,839 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 0.32 (7839 hom., cov: 31)
• Consequence: SUMF1 XM_011533624.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUMF1	XM_011533624.4	c.1015-129524T>G		intron_variant			XP_011531926.1
SUMF1	XM_017006252.3	c.955-129524T>G		intron_variant			XP_016861741.1
SUMF1	XM_017006253.2	c.940-129524T>G		intron_variant			XP_016861742.1
SUMF1	XM_017006254.3	c.1015-129524T>G		intron_variant			XP_016861743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000448413.5	c.1015-129524T>G		intron_variant, NMD_transcript_variant		2		ENSP00000404384

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48377 AN: 151764 Hom.: 7815 Cov.: 31

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.319 AC: 48452 AN: 151880 Hom.: 7839 Cov.: 31 AF XY: 0.323 AC XY: 23971 AN XY: 74200

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.330

Alfa AF: 0.316 Hom.: 3679

Bravo AF: 0.315

Asia WGS AF: 0.370 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1444056; hg19: chr3-4239953;