rs12634249

Positions:

• chr3-4444619-C-A
• chr3-4444619-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000272902.10(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 ENST00000272902.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SUMF1	NM_182760.4	c.519+4647G>T		intron_variant		ENST00000272902.10	NP_877437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUMF1	ENST00000272902.10	c.519+4647G>T		intron_variant		1	NM_182760.4	ENSP00000272902	P1

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

Gnomad4 AFR AF: 0.0843

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.174

Alfa AF: 0.226 Hom.: 5901

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12634249; hg19: chr3-4486303;