3-4334990-C-T

Variant names:

• chr3-4334990-C-T
• rs308738
• ENST00000448413.5:n.1014+41340G>A

Variant summary

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

The ENST00000448413.5(SUMF1):​n.1014+41340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,966 control chromosomes in the GnomAD database, including 5,989 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 0.27 (5989 hom., cov: 32)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMF1	XM_011533624.4	c.1014+41340G>A		intron_variant	Intron 8 of 9		XP_011531926.1
SUMF1	XM_017006252.3	c.954+75875G>A		intron_variant	Intron 7 of 8		XP_016861741.1
SUMF1	XM_017006253.2	c.939+41340G>A		intron_variant	Intron 7 of 8		XP_016861742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000448413.5	n.1014+41340G>A		intron_variant	Intron 8 of 12	2		ENSP00000404384.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40985 AN: 151848 Hom.: 5989 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.270 AC: 40986 AN: 151966 Hom.: 5989 Cov.: 32 AF XY: 0.268 AC XY: 19886 AN XY: 74260

African (AFR) AF: 0.168 AC: 6960 AN: 41420

American (AMR) AF: 0.242 AC: 3701 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1048 AN: 3466

East Asian (EAS) AF: 0.256 AC: 1324 AN: 5166

South Asian (SAS) AF: 0.437 AC: 2104 AN: 4818

European-Finnish (FIN) AF: 0.298 AC: 3151 AN: 10560

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21931 AN: 67956

Other (OTH) AF: 0.255 AC: 536 AN: 2106

Alfa AF: 0.239 Hom.: 1006

Bravo AF: 0.255

Asia WGS AF: 0.359 AC: 1248 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.10
DANN	Benign	0.74
PhyloP100		-1.8
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: rs308738; hg19: chr3-4376674;