rs1596472

Positions:

• chr3-4121878-G-A
• chr3-4121878-G-C

Variant summary

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

The XM_011533624.4(SUMF1):​c.1015-53133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 151,776 control chromosomes in the GnomAD database, including 2,437 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 0.16 (2437 hom., cov: 32)
• Consequence: SUMF1 XM_011533624.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUMF1	XM_011533624.4	c.1015-53133C>T		intron_variant			XP_011531926.1
SUMF1	XM_017006252.3	c.955-53133C>T		intron_variant			XP_016861741.1
SUMF1	XM_017006253.2	c.940-53133C>T		intron_variant			XP_016861742.1
SUMF1	XM_017006254.3	c.1015-53133C>T		intron_variant			XP_016861743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000448413.5	n.1015-53133C>T		intron_variant		2		ENSP00000404384.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24000 AN: 151658 Hom.: 2433 Cov.: 32

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.158 AC: 24011 AN: 151776 Hom.: 2437 Cov.: 32 AF XY: 0.158 AC XY: 11744 AN XY: 74192

Gnomad4 AFR AF: 0.0421

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0979

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.149

Alfa AF: 0.184 Hom.: 378

Bravo AF: 0.147

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.54
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1596472; hg19: chr3-4163562;