chr3-4121878-G-A

Variant names:

• chr3-4121878-G-A
• rs1596472
• ENST00000448413.5:n.1015-53133C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000448413.5(SUMF1):​n.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 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• mucosulfatidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SUMF1	XM_011533624.4	c.1015-53133C>T		intron_variant	Intron 8 of 9		XP_011531926.1
SUMF1	XM_017006252.3	c.955-53133C>T		intron_variant	Intron 7 of 8		XP_016861741.1
SUMF1	XM_017006253.2	c.940-53133C>T		intron_variant	Intron 7 of 8		XP_016861742.1
SUMF1	XM_017006254.3	c.1015-53133C>T		intron_variant	Intron 8 of 9		XP_016861743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000448413.5	n.1015-53133C>T		intron_variant	Intron 8 of 12	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

African (AFR) AF: 0.0421 AC: 1742 AN: 41398

American (AMR) AF: 0.173 AC: 2635 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 477 AN: 3468

East Asian (EAS) AF: 0.112 AC: 580 AN: 5166

South Asian (SAS) AF: 0.0979 AC: 468 AN: 4782

European-Finnish (FIN) AF: 0.254 AC: 2666 AN: 10514

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14966 AN: 67890

Other (OTH) AF: 0.149 AC: 314 AN: 2104

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
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1596472; hg19: chr3-4163562;