rs12634249

Variant names:

• chr3-4444619-C-A
• rs12634249
• NM_182760.4:c.519+4647G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-4444619-C-A
• chr3-4444619-C-T

Variant summary

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

The NM_182760.4(SUMF1):​c.519+4647G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,044 control chromosomes in the GnomAD database, including 3,402 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 0.20 (3402 hom., cov: 32)
• Consequence: SUMF1 NM_182760.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 10 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUMF1	NM_182760.4	c.519+4647G>T		intron_variant	Intron 3 of 8	ENST00000272902.10	NP_877437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000272902.10	c.519+4647G>T		intron_variant	Intron 3 of 8	1	NM_182760.4	ENSP00000272902.5

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30214 AN: 151928 Hom.: 3405 Cov.: 32

Gnomad AFR AF: 0.0846

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.199 AC: 30216 AN: 152044 Hom.: 3402 Cov.: 32 AF XY: 0.201 AC XY: 14968 AN XY: 74330

African (AFR) AF: 0.0843 AC: 3499 AN: 41482

American (AMR) AF: 0.281 AC: 4296 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3464

East Asian (EAS) AF: 0.205 AC: 1063 AN: 5176

South Asian (SAS) AF: 0.250 AC: 1208 AN: 4824

European-Finnish (FIN) AF: 0.266 AC: 2805 AN: 10536

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16194 AN: 67966

Other (OTH) AF: 0.174 AC: 368 AN: 2116

Alfa AF: 0.224 Hom.: 8747

Bravo AF: 0.196

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	8.9
DANN	Benign	0.68
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12634249; hg19: chr3-4486303;