rs310696

Variant names:

• chr3-4273086-A-G
• rs310696
• ENST00000448413.5:n.1014+103244T>C

Variant summary

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

The ENST00000448413.5(SUMF1):​n.1014+103244T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 148,884 control chromosomes in the GnomAD database, including 5,003 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 0.22 (5003 hom., cov: 29)
• Consequence: SUMF1 ENST00000448413.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.680
• 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

ENSG00000286579 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMF1	XM_011533624.4	c.1014+103244T>C		intron_variant	Intron 8 of 9		XP_011531926.1
SUMF1	XM_017006252.3	c.954+137779T>C		intron_variant	Intron 7 of 8		XP_016861741.1
SUMF1	XM_017006253.2	c.939+103244T>C		intron_variant	Intron 7 of 8		XP_016861742.1
SUMF1	XM_017006254.3	c.1014+103244T>C		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.1014+103244T>C		intron_variant	Intron 8 of 12	2		ENSP00000404384.1
ENSG00000286579	ENST00000653118.1	n.67-2042T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33194 AN: 148862 Hom.: 5004 Cov.: 29

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.223 AC: 33207 AN: 148884 Hom.: 5003 Cov.: 29 AF XY: 0.225 AC XY: 16362 AN XY: 72606

African (AFR) AF: 0.418 AC: 17029 AN: 40726

American (AMR) AF: 0.156 AC: 2318 AN: 14826

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3464

East Asian (EAS) AF: 0.255 AC: 1304 AN: 5118

South Asian (SAS) AF: 0.381 AC: 1819 AN: 4776

European-Finnish (FIN) AF: 0.117 AC: 1096 AN: 9332

Middle Eastern (MID) AF: 0.150 AC: 42 AN: 280

European-Non Finnish (NFE) AF: 0.126 AC: 8527 AN: 67412

Other (OTH) AF: 0.194 AC: 397 AN: 2042

Alfa AF: 0.178 Hom.: 378

Bravo AF: 0.229

Asia WGS AF: 0.330 AC: 1135 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.33
DANN	Benign	0.28
PhyloP100		-0.68
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: rs310696; hg19: chr3-4314770;