ENST00000470751.5:n.697-28986T>C

Variant names:

• chr3-3731447-A-G
• rs7628234
• ENST00000470751.5:n.697-28986T>C

Variant summary

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

The ENST00000470751.5(SUMF1):​n.697-28986T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 101,806 control chromosomes in the GnomAD database, including 13,370 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 0.61 (13370 hom., cov: 31)
• Consequence: SUMF1 ENST00000470751.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 1 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

LOC100130207 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100130207	NR_149025.1	n.697-28986T>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000470751.5	n.697-28986T>C		intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes AF: 0.608 AC: 61799 AN: 101662 Hom.: 13329 Cov.: 31

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.608 AC: 61914 AN: 101806 Hom.: 13370 Cov.: 31 AF XY: 0.608 AC XY: 30266 AN XY: 49772

African (AFR) AF: 0.630 AC: 22809 AN: 36190

American (AMR) AF: 0.590 AC: 5365 AN: 9092

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1086 AN: 1914

East Asian (EAS) AF: 0.663 AC: 2648 AN: 3994

South Asian (SAS) AF: 0.634 AC: 1956 AN: 3086

European-Finnish (FIN) AF: 0.614 AC: 4061 AN: 6618

Middle Eastern (MID) AF: 0.558 AC: 87 AN: 156

European-Non Finnish (NFE) AF: 0.587 AC: 22878 AN: 38994

Other (OTH) AF: 0.591 AC: 813 AN: 1376

Alfa AF: 0.359 Hom.: 8360

Bravo AF: 0.408

Asia WGS AF: 0.475 AC: 1637 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.72
PhyloP100		0.26

Splicing

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

Other links and lift over

dbSNP: rs7628234; hg19: chr3-3773131;