rs2587949

chr3-4181932-C-G

Variant summary

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

The XM_011533624.4(SUMF1):c.1015-113187G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,038 control chromosomes in the GnomAD database, including 17,439 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 0.48 (17439 hom., cov: 32)
• Consequence: SUMF1 XM_011533624.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUMF1	XM_011533624.4	c.1015-113187G>C		intron_variant
SUMF1	XM_017006252.3	c.955-113187G>C		intron_variant
SUMF1	XM_017006253.2	c.940-113187G>C		intron_variant
SUMF1	XM_017006254.3	c.1015-113187G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUMF1	ENST00000448413.5	c.1015-113187G>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72305 AN: 151918 Hom.: 17395 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.476 AC: 72409 AN: 152038 Hom.: 17439 Cov.: 32 AF XY: 0.479 AC XY: 35548 AN XY: 74290

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.465

Alfa AF: 0.462 Hom.: 2026

Bravo AF: 0.485

Asia WGS AF: 0.518 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.8
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2587949; hg19: chr3-4223616;